gebhart/patrepeval huggingface dataset:
Association of a polymorphism in amphiregulin with worse prognosis in metastatic colorectal cancer patients treated with cetuximab. (2013)

e14543 Background: Accumulating data suggests that Amphiregulin (AREG) and Epiregulin (EREG), ligands of the EGFR pathway, are potential prognostic and predictive markers in metastatic colorectal cancer (mCRC). Elevated AREG and EREG gene expression levels are predictive of improved response rates in mCRC patients treated with cetuximab and longer overall survival (OS) in patients with mCRC who did not receive cetuximab. Since polymorphisms in AREG and EREG may affect their expression or function, we tested whether AREG and EREG polymorphisms were associated with clinical outcome in mCRC patients treated with cetuximab. Methods: Seventy-three patients (n=73) with histopathologically-confirmed mCRC with Kras/Braf wild type were enrolled in Italy. These patients were treated with cetuximab monotherapy or irinotecan plus cetuximab as second or third line treatment. Genomic DNA was extracted from blood and 4 SNPs in AREG and 5 SNPs in EREG were analyzed by direct DNA-sequencing. Results: The median follow-up period was 13.3 months in this cohort. The median progression-free survival (PFS) and OS were 5.2 and 12.9 months respectively. The results indicate that the intronic AREG polymorphism rs28364983 A/C was associated with shorter PFS and OS. Patients with homozygous C/C (n=2) showed a median PFS of 2.3 months vs. 5.3 months for patients harboring at least one-A allele (n=71) (HR: 4.26 [95%CI: 0.98-18.5], p=0.05). Patients with homozygous C/C showed a median OS of 3.0 months vs. 13.1 months for patients harboring at least one-A allele (HR: 3.98 [95%CI: 0.93-16.9], p=0.062). An independent cohort of thirty-three patients was used to validate these initial findings and showed that patients with homozygous C/C (n=3) had a median PFS of 2.3 months vs. 3.8 months for patients harboring at least one-A allele (n=103) (HR: 3.79 [95%CI: 1.16-12.3], p=0.027) and a median OS of 3.0 months vs. 8.4 months (HR: 3.01 [95%CI: 0.93-9.71], p=0.065), respectively. Conclusions: AREG rs28364983 predicted worse outcome in mCRC patients treated with cetuximab; however, further analyses are necessary to understand the mechanism and further validate the prognostic and/or predictive role of this polymorphism.
Perovskite based gas sensors: thin-film versus capillary-filled microchannel designs (2021)

In the area of environmental monitoring, Volatile Organic Compounds (VOCs) have become a major concern. Specifically, in indoor environments, VOCs have been found to be linked with various health conditions-ranging from benign to lethal. Early detection of VOC gases can play a crucial role in ensuring a safe environment. In this work, we have looked into two different geometrical arrangements of methylammonium lead iodide (MAPbI<sub>3</sub>) perovskite to study how their selectivity and sensitivity towards an array of VOC gases under different illumination conditions may be affected. For the purpose of a comparative study, we tested the sensitivity of the device using two different photo-resistor designs, namely, (a) capillary-filled microchannels, where microchannels were created on indium tin oxide (ITO) coated plastic substrate, and leveraging the capillary motion force the microchannels were filled with the perovskite precursor solution, and (b) thin-film approach, where perovskite layers were spin coated on substrates with two conductive pads across. Samples of both designs were exposed to four analytes: acetone, ethanol, isopropanol, and methanol. In our previous study on the capillary design, we reported a decrease in photocurrent by about 22% upon exposure to methanol under illuminated conditions. The goal of this comparative study is to identify the viability of the photo-resistor design for fabricating a low-cost and fast-response gas sensor for the purpose of environmental monitoring.
Faculty Opinions recommendation of Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33. (2018)

Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor that detected proteolytic activities associated with various environmental allergens across four kingdoms, including fungi, house dust mites, bacteria and pollens. When exposed to allergen proteases, IL-33FL was rapidly cleaved in its central 'sensor' domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells. Preventing cleavage of IL-33FL reduced allergic airway inflammation. Our findings reveal a molecular mechanism for the rapid induction of allergic type 2 inflammation following allergen exposure, with important implications for allergic diseases. PMID: 29556000
Abstract 14726: Sortilin 1 is a Novel Inducer of Vascular Calcification via a Phosphate-Dependent Mechanism (2012)

Background. Vascular calcification is a prominent feature of chronic inflammatory disorders such as chronic renal disease (CRD) and atherosclerosis, and has no medical therapies. Human genome wide ...
Successor Uncertainties: Exploration and Uncertainty in Temporal Difference Learning (2018)

Posterior sampling for reinforcement learning (PSRL) is an effective method for balancing exploration and exploitation in reinforcement learning. Randomised value functions (RVF) can be viewed as a promising approach to scaling PSRL. However, we show that most contemporary algorithms combining RVF with neural network function approximation do not possess the properties which make PSRL effective, and provably fail in sparse reward problems. Moreover, we find that propagation of uncertainty, a property of PSRL previously thought important for exploration, does not preclude this failure. We use these insights to design Successor Uncertainties (SU), a cheap and easy to implement RVF algorithm that retains key properties of PSRL. SU is highly effective on hard tabular exploration benchmarks. Furthermore, on the Atari 2600 domain, it surpasses human performance on 38 of 49 games tested (achieving a median human normalised score of 2.09), and outperforms its closest RVF competitor, Bootstrapped DQN, on 36 of those.
Domain descriptions (2002)

Ideas about the meaning of descriptions, aimed at clarifying the relationship between a formal specification and the domain of the system to be specified, are introduced. Understanding of specifications must rest on explicit statements of what they are about and what they assert. The authors argue that current formal specification techniques are inadequate in this respect, and therefore cannot offer a satisfactory foundation for automated support of software development. An approach that offers a possible basis for effective reuse of descriptions generally, and of partial specifications in particular, is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Langmuir monolayers of a cholesterol-armed cyclen complex that can control enantioselectivity of amino acid recognition by surface pressure (2011)

The cholesterol-armed cyclen Na(+) complex formed stable Langmuir monolayers at the air-water interface. The π-A isotherm displayed a reasonable limiting molecular area of ∼1.57 nm(2) and the areas expanded when amino acids were dissolved in water, indicating the efficient accommodation in the monolayers. Brewster angle microscopy (BAM) images exhibited almost no defects of the compressed Langmuir monolayers regardless of the presence of amino acids. Based on the idea that the increase in the limiting molecular areas corresponds to the amount of the adsorbed amino acid, the binding constants of three enantiomeric amino acids, namely valine (Val), leucine (Leu), and phenylalanine (Phe), were calculated at different surface pressures. Remarkably, a surface pressure dependent enantioselectivity of amino acid recognition was observed. Upon compression of the monolayers, the binding constants of amino acids increased accompanying an inversion of chiral selectivity from the D- to L-form in the case of Val and, conversely, from L- to D-form in the case of Phe.
Applications of the energy-imaging integrated deconvolution algorithm for source chatracterization (2009)

The energy-imaging integrated deconvolution (EIID) algorithm is capable of deconvolving the source image at any specific energy, as well as the incident spectrum from any direction. This spectrum-image reconstruction method takes place in integrated spatial and energy domain using the maximum likelihood expectation maximization (MLEM) algorithm. This technique has been demonstrated for combined two-, three- and four-interaction Compton events from an array of 2 cm × 2 cm × 1.5 cm detectors in our previous work. By including Compton continuum events in the system model and using a sensitivity image to correct efficiency effects, the MLEM solution estimates the true incident gamma-ray spectrum with correct branching ratio. For each direction, we can then identify the source isotope based on the peak energy and relative peak area. After identifying the source isotope, the source activity can be estimated. From the reconstructed image and change of the relative peak areas from the branching ratio, the presence of shielding and the material and thickness of shielding can be estimated.
Molecular domains of the cellulose/xyloglucan network in the cell walls of higher plants (1999)

Cellulose and xyloglucan (XG) assemble to form the cellulose/XG network, which is considered to be the dominant load-bearing structure in the growing cell walls of non-graminaceous land plants. We have extended the most commonly accepted model for the macromolecular organization of XG in this network, based on the structural and quantitative analysis of three distinct XG fractions that can be differentially extracted from the cell walls isolated from etiolated pea stems. Approximately 8% of the dry weight of these cell walls consists of XG that can be solubilized by treatment of the walls with a XG-specific endoglucanase (XEG). This material corresponds to an enzyme-susceptible XG domain, proposed to form the cross-links between cellulose microfibrils. Another 10% of the cell wall consists of XG that can be solubilized by concentrated KOH after XEG treatment. This material constitutes another XG domain, proposed to be closely associated with the surface of the cellulose microfibrils. An additional 3% of the cell wall consists of XG that can be solubilized only when the XEG- and KOH-treated cell walls are treated with cellulase. This material constitutes a third XG domain, proposed to be entrapped within or between cellulose microfibrils. Analysis of the three fractions indicates that metabolism is essentially limited to the enzyme-susceptible domain. These results support the hypothesis that enzyme-catalyzed modification of XG cross-links in the cellulose/XG network is required for the growth and development of the primary plant cell wall, and demonstrate that the structural consequences of these metabolic events can be analyzed in detail.
Abstract 377: The China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Prospective Study of Percutaneous Coronary Intervention: Study Design (2015)

Background: The volume of percutaneous coronary intervention (PCI) in China has increased more than 20-fold over the last decade. Consequently, there is a need for national-level information to characterize indications for PCI and its long-term outcomes, including health status improvement, which is the principal goal of PCI in stable patients. Objectives: To conduct a nationwide prospective study of patients receiving PCI and follow them to 1) measure long-term clinical outcomes, patient-reported outcomes (PROs), risk factor control and adherence to medications for secondary prevention; 2) determine patient- and hospital-level factors associated with these outcomes; and 3) assess indications for and appropriateness of the PCI procedures performed. Methods: The China PEACE Prospective Study of PCI, conducted from December 2012 to December 2014, has recruited 5000 consecutive patients undergoing PCI for any indication from 36 representative hospitals across China and followed them for 1-year. The follow-up rate at 12 months was 94%. After obtaining informed consent from each patient, we abstracted details of their medical history, treatments, and in-hospital outcomes from medical charts. We conducted baseline interviews to characterize patient demographics, risk factors, clinical presentation, and healthcare utilization. In addition, we used several validated instruments to measure PROs describing quality of life, symptoms, mood and sleep. The primary outcome, a composite measure of death, myocardial infarction and/or revascularization, was assessed at follow-up interviews conducted at 1-, 6- and 12-months after discharge. In addition, we measured PROs, medication adherence and risk factor control at these interviews. Blood and urine samples were collected at the 1- and 12-month interviews and stored for future analysis. To establish the appropriateness of PCI, the angiograms of 2000 randomly selected patients were reviewed by independent “core” labs in China and the United States. To complement these patient-level data, we surveyed participating hospitals to characterize their facilities, processes and organizational learning culture. Conclusion: This study will generate novel, high-quality, and comprehensive national data characterizing the patient experience after PCI in China.
Monoclonal antibodies in clinical hematology and oncology. (2007)

The application of highly specific mAbs with minimal side effects in cancer therapy was, for a long time, a major goal for many clinical oncologists. Since their arrival in the clinical setting, mAbs have come to represent a standard therapy for some tumors, and have proven to be an important extension to the treatment of a broad spectrum of malignancies. The future development of mAbs for targeting alone (ie, for labeling of tumors) is insufficient for obtaining a suitable clinical response, and adequate clinical success can only be achieved by arming mAbs and targeting them to functionally significant tumor antigens such as tumor growth-related receptors. This review provides an overview of the functional characteristics of mAbs, together with some important examples of their clinical application. While mAbs may not be the 'magic bullets' that many researchers had hoped for, they are nevertheless becoming an indispensable pillar of tumor therapy.
Venous clots: evaluation with MR imaging. (1987)

In vitro and in vivo studies were performed to determine the proton relaxation and imaging characteristics of static blood and acute and organized clot in canine jugular veins. In vivo, it was found that two inversion recovery sequences using a short inversion time (100 msec) demonstrated better differentiation of signal intensity of intravascular clot from surrounding soft tissues than did standard T1- and T2-weighted sequences. In vitro, quantitative measurements showed marked reduction of both T1 and T2 relaxation time of acute clot compared with stagnant blood. In addition, the T1 relaxation time, and to a lesser extent the T2 relaxation time, shortened as the clot aged, indicating a potential role for magnetic resonance imaging in determining the age of venous thrombi.
Evaluation of a Novel Cystoscopic Compatible Cryocatheter for the Treatment of Bladder Cancer (2020)

BACKGROUND: As the acceptance of cryoablative therapies for the treatment of non-metastatic cancers continues to grow, avenues for novel cryosurgical technologies and approaches have opened. Within the field of genitourinary tumors, cryosurgical treatments of bladder cancers remain largely investigational. Current modalities employ percutaneous needles or transurethral cryoballoons or sprays, and while results have been promising, each technology is limited to specific types and stages of cancers. OBJECTIVE: This study evaluated a new, self-contained transurethral cryocatheter, FrostBite-BC, for its potential to treat bladder cancer. METHODS: Thermal characteristics and ablative capacity were assessed using calorimetry, isothermal analyses, in vitro 3-dimensional tissue engineered models (TEMs), and a pilot in vivo porcine study. RESULTS: Isotherm assessment revealed surface temperatures below – 20°C within 9 sec. In vitro TEMs studies demonstrated attainment of ≤– 20°C at 6.1 mm and 8.2 mm in diameter following single and double 2 min freezes, respectively. Fluorescent imaging 24 hr post-thaw revealed uniform, ablative volumes of 326.2 mm 3 and 397.9 mm 3 following a single or double 2 min freeze. In vivo results demonstrated the consistent generation of ablative areas. Lesion depth was found to correlate with freeze time wherein 15 sec freezes resulted in ablation confined to the sub-mucosa and ≥30 sec full thickness ablation of the bladder wall. CONCLUSIONS: These studies demonstrate the potential of the FrostBite-BC cryocatheter as a treatment option for bladder cancer. Although preliminary, the outcomes of these studies were encouraging, and support the continued investigation into the potential of the FrostBite-BC cryocatheter as a next generation, minimally invasive cryoablative technology.
Response to A+CHP by CD30 expression in the ECHELON-2 trial. (2019)

7538 Background: Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. The ECHELON-2 (E-2) study demonstrated significantly longer progression-free and overall survival with BV plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP in frontline treatment of patients (pts) with CD30+ peripheral T-cell lymphoma (PTCL). Complete remission (CR) rate (A+CHP 68%; CHOP 56%) and objective response rate (ORR) (A+CHP 83%; CHOP 72%) were also significantly increased. Expression of CD30 is universal in systemic anaplastic large-cell lymphoma (sALCL) but variable among non-sALCL subtypes. As ORR is a direct measure of antitumor activity, we examined response to A+CHP by CD30 expression. Methods: Pts with CD30+ (≥10% by local review) PTCL were included in E-2. Eligible histologies included ALK+ sALCL (IPI ≥2), ALK− sALCL, PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma, enteropathy-associated T-cell lymphoma, and hepatosplenic T-cell lymphoma. We analyzed the relationship between CD30 expression (IHC Ber H2 antibody) above and below the median (median CD30=18% PTCL-NOS; 25% AITL) and CR rate, ORR, and duration of CR (DOCR) in pts with AITL and PTCL-NOS treated with A+CHP. Results: Most (26/29, 90%) AITL pts had CD30 expression between 10% and 30%. PTCL-NOS pts were more evenly distributed across levels of CD30 expression ranging from 10% to 100%. CD30 levels were neither predictive of response (Table) nor significantly associated with DOCR in pts with AITL (P=0.30) or PTCL-NOS (P=0.90) (log-rank test). Response by CD30 expression. Clinical trial information: NCT01777152. Conclusions: CD30 expression above vs below median (or at 10%) did not predict response to A+CHP in E-2 non-ALCL subtypes, as responses were seen across CD30 levels. This may be due to intra- and inter-tumoral heterogeneity of CD30 expression, limitations of IHC, the nature of CD30 on the cell surface, and multiple mechanisms of action of BV. Further evaluation of the expression-response relationship in PTCL pts with CD30 &lt;10% is warranted.[Table: see text]
Mining High‐Throughput Screening Data by Novel Knowledge‐Based Optimization Analysis (2009)

This chapter contains sections titled: Introduction KOA Algorithm—Concept, Validation, and Its Applications in Target Identifi cation Applications of the KOA Approach in Small-Molecule HTS Data Mining Other Related Approaches for Biological Data Mining Conclusion References
Vegetable Oil Based Rigid Foam Composites (2011)

This chapter contains sections titled: Rigid Foam Composites Biofoams Production Methods Reinforcement Effects Applications/Case Study
Isotopic effects in water dication fragmentation (2005)

We investigate fast, highly charged ion-induced HOD molecule fragmentation dynamics. Focusing on double ionization of the molecule, we evidence a strong preferential cleavage of the O–H bond rather than the O–D bond. We find an isotopic branching ratio defined as the number of H+ + OD+ over D+ + OH+ dissociations of 6.5 ± 0.5. Moreover, the coincident measurement, by imaging techniques, of high-resolution kinetic energy release (KER) distributions for different fragmentation channels shows, for the first time, a clear difference of approximately 1 eV between the mean KER value of the two-body dication fragmentation channels H+ + OD+ and D+ + OH+. We analyse the two aspects of this isotopic effect by means of a semi-classical calculation simulating the dissociation dynamics via the dication electronic ground state. The final pathway is found to be strongly correlated to the initial position and momentum distributions. Those correlations explain both the observed O–H bond preferential cleavage and, for a large part, the different mean KER values. The other part of the 1 eV kinetic energy difference results from different vibrational energies of the residual molecular fragment that have also been estimated.
Hearing Results of Type IV Tympanoplasty (2014)

We evaluated the postoperative hearing results of 33 patients who underwent a type IV tympanoplasty between January 2001 and March 2010 at Tokyo Medical University Hospital.A total of 33 ears in 18 male and 15 female patients were studied with ages ranging from 8 to 77 years. The patients were followed up for at least 6 months after surgery. The surgical techniques were Type IV-c in 32 ears, and IV-i in 1 ear.In the case of a non-inflammatory disease, such as malformation of the middle ear, traumatic lesion of the ossicular chain and congenital cholesteatoma, successful hearing results were attained in 92.9% of the patients. In the case of an inflammatory disease, such as acquired cholesteatoma and otitis media, successful hearing results were attained in 36.8%.The success rate was 87.5%, when an autograft cartilage was used for an ossiculoplasty and 43.8%, when bone was used.
Temporal analyses of CRISPR-directed gene editing on NRF2, a clinically relevant human gene involved in chemoresistance (2019)

Abstract Recent data suggest that a time lag exists between nuclear penetration and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-directed gene editing activity in human cells. As CRISPR/Cas approaches clinical implementation, it is critical to establish a biological time frame in which the complex enters the cell and nucleus and executes its gene editing function. We are developing CRISPR-directed gene editing for the treatment of non-small cell lung carcinoma focusing Nuclear Factor Erythroid 2-Related Factor-Like (NRF2), a transcription factor which regulates chemoresistance. In this report, we define cellular events that surround the initialization of CRISPR-directed gene editing as a function of time. We analyze the efficiency of cellular transfection of both components of the RNP particle and assess the emergence of indels. For the first time, we image the nuclear positioning of the tracrRNA and Cas9 as a complex and as individual gene editing components. Our results indicate that while the nuclear localization of the CRISPR/Cas complex is efficient and rapid, disruption of the NRF2 gene appears four to eight hours later. We reveal an initial snapshot of the schedule and processing of CRISPR/Cas in a lung cancer cell; information that will be useful as cell-based protocols are designed and advanced.