gebhart/patrepeval huggingface dataset:
Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis (2011)

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn’t significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren’t without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren’t without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interest.
Results of two types of averaging for distortion product otoacoustic emission measurement (2002)

In a previous paper, the potential advantages of synchronous averaging in the measurement of distortion produce otoacoustic emissions were presented. In this work, the authors compare measurements using both methods. The superior signal to noise ratio and improved sensitivity of synchronous averaging is observed in the experiments.
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes (2022)

Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10<sup>-09</sup>), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease.
Long-term follow-up of the PI3Kδ inhibitor TGR-1202 to demonstrate a differentiated safety profile and high response rates in CLL and NHL: Integrated-analysis of TGR-1202 monotherapy and combined with ublituximab. (2016)

7512 Background: TGR-1202 is a novel, once-daily PI3Kδ inhibitor with a differentiated safety profile from other PI3Kδ inhibitors, and demonstrated activity in patients (pts) with advanced hematologic malignancies. An integrated-analysis is presented of pts dosed with TGR-1202 monotherapy or combined with the glycoengineered CD20 mAb ublituximab (UTX). Methods: There were no limits on prior therapies (Tx). TGR-1202 was escalated in 3 + 3 design with expansion cohorts explored. The primary endpoint was safety and efficacy was a secondary endpoint. Results: A total of 152 pts (81 monotherapy/71 combined with UTX), including 41 Follicular (FL), 40 CLL/SLL, 38 DLBCL, 11 Marginal Zone (MZL), 9 Hodgkins (HL), 8 Mantle Cell (MCL) and 5 other, were exposed to at least one dose of TGR-1202. Median age 65 yrs (22-86); 100 M/52 F; median # prior Tx = 3 (1-14); 53% refractory to immediate prior Tx. Most frequent reported AE's (all grades; Gr 3/4): nausea (44%; 1%), diarrhea (42%; 2%), fatigue (36%; 3%), vomiting (23%; 0%) and neutropenia (19%; 16%). AST/ALT increase was 6% (3% Gr 3/4), pneumonia 6% (5% Gr 3/4) and pneumonitis 1% (<1% Gr 3/4). 64 pts received TGR-1202 for 6+ mos, 33 for 1+ year, with longest on 30+ mos. Discontinuations due to AE’s occurred in 8% of pts. 109 pts received the therapeutic targeted dose and were evaluable for efficacy. Median PFS for TGR-1202 monotherapy was 24 mos and 27 mos in CLL and iNHL, respectively. Median PFS for TGR-1202 + UTX has not been reached for either CLL or iNHL. Majority of DLBCL responses occurred with TGR-1202 + UTX, including 3 CR’s and majority were of GCB subtype. Conclusions: TGR-1202 has exhibited a markedly differentiated safety profile from other PI3Kδ inhibitors to date with few discontinuations due to AE’s and limited G 3/4 events. Robust activity was observed in CLL and iNHL. Phase 2 and 3 trials are ongoing both alone and in combo with UTX in CLL, DLBCL, and iNHL. Clinical trial information: NCT01767766. Clinical trial information: NCT02006485.Disease Pts n CR n (%) PR n (%) ORR n (%) CLL/SLL 27 1 (4) 23* (85) 24 (89) iNHL (FL, MZL) 37 4 (11) 14 (38) 18 (49) aNHL (DLBCL, MCL, Richters) 37 3 (8) 6 (16) 9 (24) HL 8 - 1 (13) 1 (13) * 6/23 with persistent lymphocytosis; all on monotherapy.
High-Temperature Static and Dynamic Reliability Study of 4H-SiC Vertical-Channel JFETs for High-Power System Applications (2008)

In this work we report the most recent high-temperature long-term reliability results of the 600 V/14 A, 4H-SiC vertical-channel junction field-effect transistors (VJFETs). Two groups (A and B) devices were subjected to different thermal and electrical stresses. One device (Group A) reached 12,000 hours of continuous switching without a single failure. Four devices in Group A were thermally stressed at 250 °C over 4,670 hours in air, for which standard deviation of the specific on-resistance (RONSP) in linear region at gate bias (VGS) of 3 V were &lt; 4.1% throughout the entire duration time. The off-state characteristics were evaluated by high temperature reverse bias (HTRB) tests. Three devices (Group A) were biased at 50% rated BVDS at 250 °C for 2,278 hours. A higher reverse bias at 80 % rated BVDS was then applied to 14 devices (group B) at 200 °C for 1,000 hours. Variations of the leakage current were negligible throughout the entire HTRB test for all tested devices.
Short-circuit characterization of 10 kV 10A 4H-SiC MOSFET (2016)

The short-circuit capability of a power device is highly relevant for converter design and fault protection. In this paper a 10kV 10A 4H-SiC MOSFET is characterized and its short circuit withstand capability is studied and analyzed at 6 kV DC-link voltage. The test setup for this study is also introduced as its design, especially the inductance in the switching loop, can affect the experimental results. The study aims to present insights specific to the device which are different from that of silicon (Si) based devices. During the short-circuit operation, MOSFET saturation current, I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D,sat</sub> , increases for a few microseconds before decreasing gently. Degradation of the device can be observed at pulses longer than 5.9μs. The SiC MOSFET failed after-turn off, after a pulse of 8.6μs, due to an increase in the leakage current.
Customizing MRI‐Compatible Multifunctional Neural Interfaces through Fiber Drawing (2021)

Fiber drawing enables scalable fabrication of multifunctional flexible fibers that integrate electrical, optical and microfluidic modalities to record and modulate neural activity. Constraints on thermomechanical properties of materials, however, have prevented integrated drawing of metal electrodes with low-loss polymer waveguides for concurrent electrical recording and optical neuromodulation. Here we introduce two fabrication approaches: (1) an iterative thermal drawing with a soft, low melting temperature (T<sub>m</sub>) metal indium, and (2) a metal convergence drawing with traditionally non-drawable high T<sub>m</sub> metal tungsten. Both approaches deliver multifunctional flexible neural interfaces with low-impedance metallic electrodes and low-loss waveguides, capable of recording optically-evoked and spontaneous neural activity in mice over several weeks. We couple these fibers with a light-weight mechanical microdrive (1g) that enables depth-specific interrogation of neural circuits in mice following chronic implantation. Finally, we demonstrate the compatibility of these fibers with magnetic resonance imaging (MRI) and apply them to visualize the delivery of chemical payloads through the integrated channels in real time. Together, these advances expand the domains of application of the fiber-based neural probes in neuroscience and neuroengineering.
A HISTOCHEMICAL STUDY OF ACID AND ALKALINE PHOSPHATASE IN MOUSE LIVERS DURING VARIOUS CONDITIONS MODIFYING ACTIVITY OF THE RETICULOENDOTHELIAL SYSTEM (1961)

Under conditions in which the activity of the reticuloendothelial system is enhanced, acid and alkaline phosphatase activities of the mouse liver are increased. The acid phosphatase activity is localized in Kupffer cells, whereas the increased alkaline phosphatase activity is found within the endothelial linings of sinusoids. Changes in alkaline phosphatase activity occur earlier than those in acid phosphatase activity. The increase in acid phosphatase, but not the increase in alkaline phosphatase activity, could be inhibited by cortisone. Similar changes in alkaline phosphatase activity have been observed following histamine or serotonin injections and after partial hepatectomy. Peritoneal cells from mice infected with B.C.G. strain tubercle bacilli display more acid phosphatase activity than such cells from normal mice.
Multiplexed effector screening for recognition by endogenous resistance genes using positive defense reporters in wheat protoplasts (2023)

Summary Plant resistance ( R ) and pathogen avirulence ( Avr ) gene interactions play a vital role in pathogen resistance. Efficient molecular screening tools for crops lack far behind their model organism counterparts, yet they are essential to rapidly identify agriculturally important molecular interactions that trigger host resistance. Here, we have developed a novel wheat protoplast assay that enables efficient screening of Avr/R interactions at scale. Our assay allows access to the extensive gene pool of phenotypically described R genes because it does not require the overexpression of cloned R genes. It is suitable for multiplexed Avr screening, with interactions tested in pools of up to fifty Avr candidates. We identified Avr/R-induced defense genes to create promoter-luciferase reporter. Then, we combined this with a dual-color ratiometric reporter system that normalizes read-outs accounting for experimental variability and Avr/R-induced cell-death. Moreover, we introduced a self-replicative plasmid reducing the amount of plasmid used in the assay. Our assay increases the throughput of Avr candidate screening, accelerating the study of cellular defense signaling and resistance gene identification in wheat. We anticipate that our assay will significantly accelerate Avr identification for many wheat pathogens, leading to improved genome-guided pathogen surveillance and breeding of disease-resistant crops.
Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents (2019)

A series of 2-anilinopyridyl linked benzothiazole-hydrazone conjugates (<bold>5a-aa</bold>) were designed, synthesized and evaluated for their anticancer potential.
Potent Induction of IFN-α and Chemokines by Autoantibodies in the Cerebrospinal Fluid of Patients with Neuropsychiatric Lupus (2009)

Neuropsychiatric disease in systemic lupus erythematosus (NPSLE) is a poorly understood, but potentially fatal, disease manifestation. A pathogenetic role for autoantibodies is suspected, but the mechanism is unclear. Since immune complexes in SLE can stimulate IFN-alpha and there is strong evidence in humans and in mice that IFN-alpha can cause neuropsychiatric manifestations, we asked whether NPSLE patient serum and/or cerebrospinal fluid (CSF) contain abnormally high IFN-alpha-inducing activity. In a bioassay containing plasmacytoid dendritic cells and a source of Ag, NPSLE CSF induced significantly higher IFN-alpha compared with CSF from patients with multiple sclerosis or other autoimmune disease controls. When normalized for IgG concentration, NPSLE CSF was 800-fold more potent at inducing IFN-alpha compared with paired serum due to inhibitors present in serum. Analysis of Ig-deficient patient serum, depletion of IgG from normal serum, as well as addition of purified IgG to NPSLE CSF and serum in the bioassays revealed that one inhibitor was contained within the IgG fraction itself. In addition to IFN-alpha, immune complexes formed by CSF autoantibodies produced significantly increased levels of IFN-gamma-inducible protein 10 (IP-10/CXCL), IL-8, and MCP-1, all of which have been reported to be elevated in CSF from NPSLE patients. Taken together, these findings are consistent with a two-step model of NPSLE whereby CSF autoantibodies bind to Ags released by neurocytotoxic Abs or other brain cell injury, and the resulting immune complexes stimulate IFN-alpha and proinflammatory cytokines and chemokines.
Potassium Phosphate Catalyzed Nitroaldol Reaction (2004)

Abstract Potassium phosphate was found to catalyze condensation of nitroalkanes with various aliphatic and aromatic aldehydes to form nitroaldols in excellent yields in acetonitrile medium at room temperature.
RASSF10 suppresses colorectal cancer growth by activating P53 signaling and sensitizes colorectal cancer cell to docetaxel (2015)

RASSF10 has previously been reported to be frequently methylated in a number of malignancies. To understand the importance of RASSF10 inactivation in colorectal carcinogenesis, eight colorectal cancer cell lines, 89 cases of primary colorectal cancer and 5 cases of normal colorectal mucosa were examined. Methylation specific PCR, western blot, siRNA, gene expression array and xenograft mice were employed. The expression of RASSF10 was regulated by promoter regional methylation in colorectal cancer cells. RASSF10 was methylated in 60.7% (54/89) of primary colorectal cancers and was positively associated with tumor stage (p < 0.05) and metastasis (p < 0.05). Restoration of RASSF10 led to inhibition of colorectal cancer cell proliferation in vitro and in vivo and increased apoptosis. Gene expression arrays discovered RASSF10 inhibition of MDM2 expression as a mediator of these effects, which was confirmed with RT-PCR and western blot. RASSF10 was shown to activate P53 signaling in RKO and HCT116 cells after UV exposure, and sensitized these cells to docetaxel. In conclusion, our study demonstrates RASSF10 is frequently methylated in human colorectal cancer leading to loss of expression. RASSF10 normally suppresses human colorectal cancer growth by activating P53 signaling in colorectal cancer, and restored expression sensitizes colorectal cancer to docetaxel.
ChemInform Abstract: Solid Catalysts for Multistep Reactions: One‐Pot Synthesis of 2,3‐Dihydro‐1,5‐benzothiazepines with Solid Acid and Base Catalysts. (2014)

Abstract Thioaniline and 1,3‐diphenylpropenone react to benzothiazepine in the presence of alumosilicates.
Synthesis of Open-Ended, Cylindrical Au−Ag Alloy Nanostructures on a Si/SiOx Surface (2004)

Dip-pen nanolithography (DPN) in conjunction with wet chemical etching was used to synthesize a new class of open-ended, cylindrical Au−Ag alloy nanostructures on a Si/SiOx surface. Ag nanostructures were prepared by depositing dot MHA features on Ag-coated Si/SiOx, followed by etching with ferri/ferrocyanide solution. When these Ag nanostructures are reacted with HAuCl4, electroless plating of Au occurs on the sidewalls of the silver features along with concomitant oxidation of the Ag. This results in the formation of novel open-ended, cylindrical Au−Ag alloy nanostructures. Insight into the mechanism for this process is provided.
Universal Quenching Probe System: Flexible, Specific, and Cost-Effective Real-Time Polymerase Chain Reaction Method (2009)

We have developed a flexible, specific, and cost-effective real-time polymerase chain reaction (PCR) method. In this technique, a quenching probe (QProbe) and a nonfluorescent 3'-tailed probe are used. The QProbe is a singly labeled oligonucleotide bearing a fluorescent dye that is quenched via electron transfer between the dye and a guanine base at a particular position. The nonfluorescent 3'-tailed probe consists of two parts: one is the target-specific sequence on the 5' side, and the other is complementary to the QProbe on the 3' side. When the QProbe/nonfluorescent 3'-tailed probe complex hybridizes with the target in PCR, the fluorescence of the dye is quenched. Fluorescence quenching efficiency is proportional to the amount of the target. We called this method the universal QProbe system. This method substantially reduces the cost of real-time PCR setup because the same QProbe can be used for different target sequences. Moreover, this method allows accurate quantification even in the presence of nonspecific PCR products because the use of nonfluorescent 3'-tailed probe significantly increases specificity. Our results demonstrate that this method can accurately and reproducibly quantify specific nucleic acid sequences in crude samples, comparable with conventional TaqMan chemistry. Furthermore, this method is also applicable to single-nucleotide polymorphism (SNP) genotyping.
Factors Influencing Market Adoption and Evolution of NFV/SDN Cybersecurity Solutions. Evidence from SHIELD Project (2018)

SHIELD is an EU-funded project, targeting at the design and development of a novel cybersecurity framework, with the aim of which offers security-as-a-Service in an evolved telco environment. The SHIELD framework leverages NFV (Network Functions Virtualization) and SDN (Software-Defined Networking) for virtualization and dynamic placement of virtualised security appliances in the network (virtual Network Security Functions – vNSFs), Big Data analytics for real-time incident detection and mitigation, as well as attestation techniques for securing both the infrastructure and the services. This paper presents a detail Roadmapping analysis and identifies the factors that will affect market adoption and the evolution of SHIELD or similar cybersecurity solutions.
A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand (2021)

Despite the development of next-generation antiandrogens, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. Here, we describe a unique semisynthetic bispecific antibody that uses site-specific unnatural amino acid conjugation to combine the potency of a T cell-recruiting anti-CD3 antibody with the specificity of an imaging ligand (DUPA) for prostate-specific membrane antigen. This format enabled optimization of structure and function to produce a candidate (CCW702) with specific, potent in vitro cytotoxicity and improved stability compared with a bispecific single-chain variable fragment format. In vivo, CCW702 eliminated C4-2 xenografts with as few as three weekly subcutaneous doses and prevented growth of PCSD1 patient-derived xenograft tumors in mice. In cynomolgus monkeys, CCW702 was well tolerated up to 34.1 mg/kg per dose, with near-complete subcutaneous bioavailability and a PK profile supporting testing of a weekly dosing regimen in patients. CCW702 is being evaluated in a first in-human clinical trial for men with mCRPC who had progressed on prior therapies (NCT04077021).
MAR shopping assistant usage: Delay, error, and utility (2011)

This poster will present findings from a study of a shopping assistant prototype with simulated augmented reality information. The goal of the study was to find out the acceptable level of delay in presentation of augmented information and the acceptable rate of error of the information presented. Twelve participants interacted with a Samsung Omnia™ smartphone that presented a wine shopping scenario under several levels of delay in showing product information. Participants indicated their willingness to wait for each delay they experienced. Participants also answered a survey about which types of products they would want a shopping assistant application to assist with.
Highly Specific, Fluorescent Cannabinoid Type 2 Receptor Probes Enable Applications in Microscopy, Flow Cytometry and FRET-based Binding Assays (2019)

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite its significance, researchers lack reliable tools to address questions concerning the complex mechanism of CB2R signaling and its downstream consequences, especially in cell-type and tissue-dependent contexts. Herein, we report highly specific CB2R fluorescent probes and their use in a variety of applications: flow cytometry with overexpressing as well as endogenously expressing cells, real-time confocal microscopy of living cells, and a novel FRET-based, CB2R binding assay amenable to high throughput screening.