jimnoneill/paper-to-field-training huggingface dataset:
Data from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study

Field: Medicine (Health Sciences)

<div>AbstractPurpose:<p>This phase Ib open-label, multicenter, platform study (NCT02646748) explored safety, tolerability, and preliminary activity of itacitinib (Janus kinase 1 inhibitor) or parsaclisib (phosphatidylinositol 3-kinase δ inhibitor) in combination with pembrolizumab [programmed death-1 (PD-1) inhibitor].</p>Experimental Design:<p>Patients with advanced or metastatic solid tumors with disease progression following all available therapies were enrolled and received itacitinib (Part 1 initially 300 mg once daily) or parsaclisib (Part 1 initially 10 mg once daily; Part 2 all patients 0.3 mg once daily) plus pembrolizumab (200 mg every 3 weeks).</p>Results:<p>A total of 159 patients were enrolled in the study and treated with itacitinib (Part 1, <i>n</i> = 49) or parsaclisib (Part 1, <i>n</i> = 83; Part 2, <i>n</i> = 27) plus pembrolizumab. The maximum tolerated/pharmacologically active doses were itacitinib 300 mg once daily and parsaclisib 30 mg once daily. Most common itacitinib treatment-related adverse events (TRAE) were fatigue, nausea, and anemia. Most common parsaclisib TRAEs were fatigue, nausea, diarrhea, and pyrexia in Part 1, and fatigue, maculopapular rash, diarrhea, nausea, and pruritus in Part 2. In patients receiving itacitinib plus pembrolizumab, four (8.2%) achieved a partial response (PR) in Part 1. Among patients receiving parsaclisib plus pembrolizumab, 5 (6.0%) achieved a complete response and 9 (10.8%) a PR in Part 1; 5 of 27 (18.5%) patients in Part 2 achieved a PR.</p>Conclusions:<p>Although combination of itacitinib or parsaclisib with pembrolizumab showed modest clinical activity in this study, the overall response rates observed did not support continued development in patients with solid tumors.</p>Significance:<p>PD-1 blockade combined with targeted therapies have demonstrated encouraging preclinical activity. In this phase I study, patients with advanced solid tumors treated with pembrolizumab (PD-1 inhibitor) and either itacitinib (JAK1 inhibitor) or parsaclisib (PI3Kδ inhibitor) experienced limited clinical activity beyond that expected with checkpoint inhibition alone and showed little effect on T-cell infiltration in the tumor. These results do not support continued development of these combinations.</p></div>
WNT5A expression is regulated by the status of its promoter methylation in leukaemia and can inhibit leukemic cell malignant proliferation

Field: Medicine (Health Sciences)

Although down-regulation of WNT5A expression has been reported in some types of leukaemias, the level of WNT5A expression has not been assessed in leukaemia complete remission (CR) cases, the relationship among WNT5A expression level, the status of its promoter methylation, and the curative effect of leukaemia has not been reported, and the effect of WNT5A on cell proliferation has not been assessed. In this study, we analyzed WNT5A expression in various kinds of leukaemia cases, leukaemia CR cases, non-malignant hematopoietic (NMH) cases, as well as in leukemic cell lines and CD34+ cells. The methylation status of the WNT5A promoter and the levels of the Wnt5a protein were also studied. We also investigated the effect of Wnt5a on leukemic cell proliferation. WNT5A expression level was higher in NMH but lower in leukaemia cases compared to that in CR-cases (P<0.01), and was expressed at low level in leukemic cell lines K562, U937 and Jurkat. Wnt5a protein was positive in NMH, CR cases and CD34+, but negative in leukaemia cases. WNT5A promoter was methylated in leukaemia cases and all leukemic cell lines, but not in NMH and CR cases. WNT5A expression was up-regulated after exposure to the demethylating agent 5-Aza-2'-deoxycytidine (Aza) in the K562, U937, Jurkat leukemic cell lines and in 83.3% (10/12) of CR patients after cure, respectively. The increased Wnt5a protein can inhibit K562 malignant proliferation and arrest cell cycle at the G2/M phase after exposure to Aza. These results indicate that WNT5A expression was restored in complete remission cases due to demethylation, and Wnt5a can inhibit leukaemic cell proliferation. We propose that WNT5A can act as a suppressor factor in leukemogenesis and can be used as a potential marker for curative effect assessment in leukaemia.
Studies on Feeding and Digestion in Protozoa. III. Acid Phosphatase Activity in Food Vacuoles of Paramecium multimicronucleatum

Field: Agricultural and Biological Sciences (Life Sciences)

SYNOPSIS. Acid phosphatase activity was studied in total mounts and sections of agnotobiotic Paramecium multimicronucleatum by the alpha‐naphthyl phosphate‐hexazotized rosanilin method. Timing was achieved by India ink marking of food vacuoles. Enzyme activity is present in small endoplasmic granules and in the greatest part of food vacuoles. Following an inactive stage (stage I) of an average length of 5 min the activity appears at the periphery of the vacuole, in most cases in the form of granules (stage II). A high activity level (stage III) is attained within 1 1/2 min and maintained for the most part of the vacuolar cycle. The activity disappears only in the latest vacuoles before egestion (stage IV). The appearance of activity is not concurrent with but succeeding to the maximum of vacuolar acidity as ascertained by feeding Congo red stained killed yeast cells. On the basis of these results the food vacuoles may be looked upon as belonging to the lysosomes sensu lato.
Treatment of asthma in children.

Field: Medicine (Health Sciences)

The epidemiology, etiology and pathophysiology, clinical presentation and diagnosis, and drug therapy of asthma in children are reviewed. Recent advances in drug therapy have, for unknown reasons, been accompanied by an increase in the morbidity and mortality associated with childhood asthma. The cause of asthma is not precisely understood, but an inflammatory process and hyperactivity of airways are common findings in the disease. Asthma in children can be classified as intermittent, chronic, or indeterminate; a severe, prolonged episode not relieved by usual treatment is called status asthmaticus. The hallmark symptoms of asthma are coughing, dyspnea, and wheezing. Beta-adrenergic agonists can be used orally for diagnostic purposes or for nocturnal asthma; i.v. or s.c. for emergency treatment; or by inhalation for relief of acute asthmatic episodes. Experience with anticholinergics in children is limited, and these agents should be used only when other options have failed. Inhalation of cromolyn sodium is very safe and is useful for the prophylactic treatment of mild to moderate asthma. Corticosteroids, which are used both for acute asthmatic episodes and for long-term treatment, can be given orally, i.v., or by inhalation. Theophylline is used for prophylactic therapy in children with chronic asthma. Selection of a drug regimen is based on knowledge of efficacy, pharmacokinetics, compliance, and toxicity. The treatment of asthma in children requires consideration of drug properties in young patients. Drugs used to treat childhood asthma include beta agonists, anticholinergics, cromolyn sodium, corticosteroids, and theophylline.
High-Precision Computing based on the CUDA Architecture in Residual Number Systems

Field: Computer Science (Physical Sciences)

Residual Number Systems (RNS) are recognized for their parallel arithmetic capabilities. In recent years, they have been employed in various demanding applications, including digital signal processing, high-precision computing, cryptography, and large neural networks. With the advancement of multiprocessor systems on general-purpose platforms, the utilization of RNS for the effective parallelization of arithmetic computational operations with a large dynamic range of up to several tens of bits becomes a crucial aspect. To this end, modern Graphics Processing Units (GPUs) with several thousands of computational cores are ideal platforms. This study evaluates the efficacy of using RNS for implementing multiple precision arithmetic on NVIDIA GPUs using the CUDA hardware and software parallel computing architecture. The results of the experiments demonstrate the high efficiency of RNS for the multiplication operation. A configuration of 256 modules providing a 6400-bit dynamic range results in a computation time that is 7.92 times faster compared to the implementation on the standard GMP MP variant.
Conditioned adrenocortical steroid elevations in the rat.

Field: Neuroscience (Life Sciences)

An illness-induced taste aversion paradigm was used to condition an elevation in plasma corticosterone level. Rats were injected with cyclophosphamide 30 min after consuming a novel saccharin drinking solution. Plasma corticosterone levels were measured before conditioning to determine unconditioned steroid levels and 3 and 6 days after training when conditioned and nonconditioned animals were provided with the saccharin solution or plain water, or were left deprived. The pairing of saccharin and cyclophosphamide was effective in inducing a passive avoidance response. There were no differences between the steroid levels of conditioned and nonconditioned animals supplied with plain water or those that remained deprived, although deprivation increased corticosterone levels. Nonconditioned rats presented with saccharin had steroid levels that did not differ from control values. Conditioned animals presented with saccharin showed an elevation in steroid level which was significantly greater than that observed in any other group. Comparable results were obtained when LiCl was used as the unconditioned stimulus.
DataSheet_1_Identification and Characterization of Three Spore Wall Proteins of Enterocytozoon Bieneusi.docx

Field: Immunology and Microbiology (Life Sciences)

<p>Enterocytozoon bieneusi is the most common microsporidian pathogen in farm animals and humans. Although several spore wall proteins (SWPs) of other human-pathogenic microsporidia have been identified, SWPs of E. bieneusi remain poorly characterized. In the present study, we identified the sequences of three E. bieneusi SWPs from whole genome sequence data, expressed them in Escherichia coli, generated a monoclonal antibody (mAb) against one of them (EbSWP1), and used the mAb in direct immunofluorescence detection of E. bieneusi spores in fecal samples. The amino acid sequence of EbSWP1 shares some identity to EbSWP2 with a BAR2 domain, while the sequence of EbSWP3 contains a MICSWaP domain. No cross-reactivity among the EbSWPs was demonstrated using the polyclonal antibodies generated against them. The mAb against EbSWP1 was shown to react with E. bieneusi spores in fecal samples. Using chromotrope 2R staining-based microscopy as the gold standard, the sensitivity and specificity of the direct immunofluorescence for the detection of E. bieneusi were 91.4 and 73.7%. Data generated from the study could be useful in the characterization of E. bieneusi and immunological detection of the pathogen.</p>
Modelling of the Interactions of Some Inhibitors with the PGHS‐1 by BIODOCK ‐ a Stochastic Approach to the Automated Docking of Ligands to Biomacromolecules

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

The automated stochastic docking procedure BioDock has been applied to a series of inhibitors of PGH synthase-1, the key enzyme in the synthesis of eicosanoids from arachidonic acid. Some well known inhibitors, like meclofenamic acid, flurbiprofen, piroxicam and indomethacine have been docked to the structure of the ovine enzyme, as recently obtained by means of X-ray crystallographic analysis. Two inhibitors selective towards PGHS2 (the inducible isoform, which seems to be more involved into inflammatory processes) have been also docked to PGHS-1, in order to highlight possible interaction differences.
Unruly Americans and the Origins of the Constitution. By Woody Holton. (New York: Hill and Wang, 2007. xii, 370 pp. Cloth, $27.00, ISBN 978-0-8090-8061-8.)

Field: Social Sciences (Social Sciences)

Early American historiography has sometimes suffered from a monochromatic focus on a small group of elites, as though George Washington and company invented a nation all by themselves. In Unruly Americans and the Origins of the Constitution, Woody Holton adds color to the group portrait of the Founders, and the primary color on his palette is green—the color of money. To his neo-Progressive eye, the overriding motive of the constitutional Framers was “not to safeguard civil liberties” (p. xi), but rather to protect their own and the country's financial interests. Holton privileges the arguments and efforts of “ordinary farmers” who believed the recession that followed the Revolution could have been ended “without making the United States a less democratic country,” as the Framers in fact made it (p. 17). It was they who forced upon the Framers a bill of rights, and if Americans today are grateful for their civil liberties, it is those unruly folk who agitated for the first ten amendments we should thank, not the Framers (p. xi).
Continuous Selections of the Inverse Numerical Range Map

Field: Mathematics (Physical Sciences)

For a complex $n$-by-$n$ matrix $A$, the numerical range $F(A)$ is the range of the map $f_A(x) = x^*A x$ acting on the unit sphere in $\C^n$. We ask whether the multivalued inverse numerical range map $f_A^{-1}$ has a continuous single-valued selection defined on all or part of $F(A)$. We show that for a large class of matrices, $f_A^{-1}$ does have a continuous selection on $F(A)$. For other matrices, $f_A^{-1}$ has a continuous selection defined everywhere on $F(A)$ except in the vicinity of a finite number of exceptional points on the boundary of $F(A)$.
Serum CRP and Leptin Levels to Assess Nutritional Status in Patients on Maintenance Hemodialysis

Field: Medicine (Health Sciences)

Introduction:Malnutrition is common in patients with End Stage Renal Disease (ESRD) on Hemodialysis (HD).Depending on the parameter measured, the prevalence of malnutrition in the chronic dialysis population ranges from 10 to 54%.It is related with the secretion of a number of proteins (adipokines), including leptin and adiponectin and also cytokines such as IL-6.This study was planned with the aim of reviewing the association of nutritional status with serum leptin and CRP levels in hemodialysis patients. Material and methods:The present study was conducted in the department of Medicine at Chattrapati Shivaji Subharti Hospital from August 2017 to March 2019; consisted of 50 patients of End stage Renal Disease on maintenance hemodialysis admitted in Chattrapati Shivaji Subharti Hospital during the time period.Results: Out of the 50 subjects, 35 (70%) were male and 15 (30%) were females.The Lean Body Mass (%) in the study subjects was 59.76±5.92.The overall mean leptin level distribution among the subjects was 1.51±0.36.The overall mean CRP level distribution among the subjects.was 3.75±0.47.A positive correlation was found between CRP and BMI with statistical significance as p<0.05 (table 11).Similarly a highly positive correlation was found between Leptin and BMI as p<0.01. Conclusion:Our study point to possible use of serum leptin and CRP concentration as an indicator of nutritional status in HD patients based on observed significant positive correlation between serum leptin and CRP concentrations with BMI values.
A back-reaction approach to dark energy

Field: Physics and Astronomy (Physical Sciences)

This thesis is mainly about how to set up and carry out in a physically meaningful way the idea of back-reaction, according to which dark energy could be an effective source. There are, broadly speaking, two distinct approaches. One is focused on how cosmological observables are affected by inhomogeneities, while the other is focused on a theoretical description of the inhomogeneous universe by means of a mean-field description. Both approaches, however, share the idea of smoothing out inhomogeneities. We developed this duality in the interpretation of the back-reaction by means of toy models based on the Lemaitre-Tolman-Bondi solution of Einstein's equations. In particular we focused on voids expanding faster than the background solution.
Nucleotide Sequence and Host Range of Coleus Viroid Isolated from Coleus(Coleus blumei Benth.) in Japan.

Field: Agricultural and Biological Sciences (Life Sciences)

A viroid was detected from coleus (Coleus blumei Benth.) in Japan, which was 1 nucleotide larger (249nt) than coleus blumei viroid 1 (CbVd1) and coleus yellow viroid (CYVd), indicating that the viroid was an isolate of CbVd1. Four species of plants in Labiatae (Mentha spicata, Mentha arvensis var. piperascens, Ocimum basilicum and Melissa officinalis), in addition to coleus, were first found to be infected with the CbVd1 without showing any detectable disease symptoms.
Inhibitory motor innervation of the gall bladder musculature by intrinsic neurones containing nitric oxide in the Australian Brush-tailed possum ( Trichosurus vulpecula )

Field: Neuroscience (Life Sciences)

BACKGROUND Gall bladder functions are modulated by neurones intrinsic to the organ. Data are available on the neurochemical composition of intrinsic and extrinsic nerves innervating the gall bladder but are lacking on specific functional classes of gall bladder neurones. AIMS To characterise the intrinsic motor neurones of the gall bladder and identify their roles using pharmacological techniques. METHODS Retrograde tracing from the possum gall bladder muscle in vitro allowed identification of intrinsic motor neurones. Subsequently, their content of choline acetyltransferase and nitric oxide synthase, markers of acetylcholine and nitric oxide containing neurones, was established using immunohistochemical techniques. Organ bath pharmacology was used to evaluate neurotransmission by acetylcholine and nitric oxide in gall bladder muscle strips. RESULTS Innervation of the gall bladder musculature by neurones of both the muscular and serosal plexuses was demonstrated. A large proportion (62%) of these motor neurones were immunoreactive for nitric oxide synthase. All gall bladder neurones showed immunoreactivity for choline acetyltransferase. Organ bath pharmacology confirmed the neuroanatomical data, showing acetylcholine and nitric oxide mediating neurotransmission to the gall bladder musculature. CONCLUSIONS Neurones containing acetylcholine and nitric oxide, located within the muscular and serosal plexuses, provide excitatory and inhibitory motor innervation of the gall bladder, respectively. The large inhibitory innervation suggests active relaxation of the gall bladder during filling, mediated by intrinsic nerves.
Small Bodies: Near and Far Database for thermal infrared observations of small bodies in the Solar System

Field: Physics and Astronomy (Physical Sciences)

In this paper we present the "Small Bodies: Near and Far" Infrared Database, an easy-to-use tool intended to facilitate the modeling of thermal emission of small Solar System bodies. Our database collects thermal emission measurements of small Solar Systems targets that are otherwise available in scattered sources and gives a complete description of the data, with all information necessary to perform direct scientific analyses and without the need to access additional, external resources. This public database contains representative data of asteroid observations of large surveys (e.g. AKARI, IRAS and WISE) as well as a collection of small body observations of infrared space telescopes (e.g. the Herschel Space Observatory) and provides a web interface to access this data (https://ird.konkoly.hu). We also provide an example for the direct application of the database and show how it can be used to estimate the thermal inertia of specific populations, e.g. asteroids within a given size range. We show how different scalings of thermal inertia with heliocentric distance (i.e. temperature) may affect our interpretation of the data and discuss why the widely-used radiative conductivity exponent ($α$=-3/4) might not be adequate in general, as hinted by previous studies.
CFD simulation of multiphase fluid flow in a two-dimensional gas-solid fluidized bed using two different turbulence models

Field: Chemical Engineering (Physical Sciences)

This paper presents the numerical analysis of fluid flow in a two-dimensional fluidized bed through simulations. The experiment data of Geldart B particles fluidized bed is used to validate the simulation results. Simulations has been conducted using Computational Fluids Dynamics (CFD) method, Eulerian Eulerian two fluid approach with Gidaspow drag model, kinetic theory of granular flow, and two turbulence models. Two different turbulence models of Standard (STD) k-ε and Renormalization Group (RNG) k-ε are used since they are proven applicable for high complexity flows such as in the fluidized bed. Simulations were conducted using the commercial software CFDSOF®. From the experiments obtained that the minimum fluidization velocity is 0.4 m/s and the pressure drop across the bed is around 700 Pa. Both models cannot predict the pressure drop across the bed well below the minimum fluidization velocity, but above it both models give the closer results to the experiment data and the RNG k-ε model predicts closer in comparison to the STD k-ε model. The STD k-ε model predicts the turbulent regime sooner and the static pressure distribution a little bit higher.
The Relationship Between Bonding with Nonhuman Animals and Students' Attitudes Toward Science

Field: Social Sciences (Social Sciences)

Abstract This paper examines the relationship of bonding with nonhuman animals during an interactive, animal-in-the-wild science program (Talking Talons) and the science attitudes of 358 young children between the ages of 8 and 14 Talking Talons utilizes typically wild animals such as raptors, reptiles, and bats in a school-based educational science curriculum. Qualitative data from interviews with students in the program indicated that "bonding with animals" (BWA) and the educators (BWE) within the program were related to increased positive attitudes toward science. The program used quantitative methods to examine these dual relationships—with animals and with educators- on student attitude toward science. The program performed a step-wise multiple regression with "Attitude toward Science" as the dependent variable and "Gender," "Age," and "Bonding with Animals" as independent variables. Both "Bonding with Animals" and "Bonding with the Educator" contributed significantly to prediction of the participants' science attitudes. Altogether 28% of the variance in "Science Attitude" was predicted by both "Gender" and "Age" (10%), "Bonding with Animals" (16%) and "Bonding with Educator" (2%). Bonding with the animals had a large quantifiable relationship with student attitudes toward science.