gebhart/patrepeval huggingface dataset:
Plecanatide, a Novel Uroguanylin Analog: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate Efficacy and Safety in Patients With Irritable Bowel Syndrome With Constipation (IBS-C) (2014)

Introduction: Plecanatide is a minimally absorbed peptide analog of uroguanylin, the naturally occurring ligand for the human intestinal guanylate cyclase-C receptor. The objective of this trial was to assess the safety and efficacy of a range of plecanatide doses in patients with IBS-C. Methods: We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 424 patients with IBS-C. Patients were randomly assigned to groups given 0.3, 1.0, 3.0, or 9.0 mg oral tablet plecanatide or placebo once daily for 12 weeks. The primary and secondary efficacy assessments were evaluated over 12 weeks of treatment. Primary efficacy endpoint was change from baseline in complete spontaneous bowel movements (CSBMs). Key secondary efficacy endpoints included change from baseline in worst abdominal pain intensity (0-10 point severity scale), the Food and Drug Administration’s (FDA’s) overall responder endpoint for IBS-C (responder: a patient who reported (i) improvement of ≥ 30% from baseline in average daily worst abdominal pain score and (ii) increase of ≥ 1 CSBM from baseline, both in the same week for ≥ 6/12 weeks), change in stool consistency using the Bristol Stool Form Scale (BSFS), and other secondary endpoints based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored. Results: Plecanatide 1.0, 3.0, and 9.0 mg dose groups had significantly improved weekly rates of CSBM frequency (primary endpoint) compared with placebo; the increases were 2.12, 2.74, and 2.44 for plecanatide doses 1.0, 3.0, and 9.0 mg, respectively (p ≤. 05 for each pair-wise comparison). Notably, plecanatide 3.0 mg dose significantly improved all important secondary endpoints: change from baseline in worst abdominal pain intensity, FDA overall responder endpoint, stool consistency and straining. The 9.0 mg dose demonstrated statistical improvement on the FDA overall responder endpoint, stool consistency and straining and numerical improvement on worst abdominal pain intensity. The most common adverse event was diarrhea (9.4% at 1.0 mg, 9.3% at 3.0 mg, and 11.8% at the highest 9.0 mg dose). Conclusion: Plecanatide therapy was safe and well-tolerated and produced rapid and clinically relevant improvement of bowel habits and abdominal pain in patients with IBS-C. Disclosure - Kunwar Shailubhai, Laura Barrow, Patrick Griffin, Gary Jacob are employees of Synergy Pharmaceuticals, Inc. Phil Miner is a consultant to Synergy Pharmaceuticals, Inc.
Abstract 5307: Analysis of telomere length in classic and variant hairy cell leukemia (2015)

Abstract Telomeres are ribonucleoprotein structures which protect the ends of chromosomes from aberrant recombination events and have been reported to be relatively short in several hematologic malignancies; adverse prognosis has been documented in chronic lymphocytic leukemia and several non-B-cell malignancies. However, their association with prognosis of classic and variant hairy cell leukemia (HCL and HCLv) has not been described. To study telomeres in HCL and HCLv, DNA from leukemic cells of patients was measured by monochrome multiplex quantitative PCR (MMQPCR) to determine relative telomere length (RTL). Of 46 patients in the cohort, 5 of 27 HCL (19%) vs. 12 of 19 HCLv (63%) patients had unmutated (&amp;gt;98% homology to germline sequence) immunoglobulin rearrangements (p = 0.0045). IGHV4-34+ rearrangements were present in 12 of the 17 (70%) unmutated cases, including five HCL and seven HCLv. RTL was shown to be shorter in unmutated HCL (p = 0.03) and in patients who had died of their disease (p = 0.03). RTL negatively correlated with IGHV homology to germline sequence (r = -0.331; p = 0.025), and age (r = -0.315; p = 0.035). Shorter RTL was associated with death from disease in either HCL (p = 0.0063) or HCLv (p = 0.0034), in patients with mutated IGHV rearrangements (p = 0.005), or in all patients combined (p = 0.0008). Median survival from diagnosis was less in time in patients with shorter RTL (p = 0.016) and this significant difference persisted when examining just the 19 patients with HCLv (p = 0.029). Gene expression profiling identified several genes related to telomere maintenance with significantly different expression levels between mutated and unmutated cases. This first of kind study in HCL/HCLv suggests that telomeres play a role in the relative pathology of HCL and HCLv and RTL could be used as a prognostic biomarker in gauging the indolent course of these cancers. Citation Format: Daniel C. Edelman, Evgeny Arons, Holly Stevenson, Allison Gomez, David Petersen, Hong Zhou, Yonghong Wang, Joshua J. Waterfall, Paul S. Meltzer, Robert Kreitman. Analysis of telomere length in classic and variant hairy cell leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5307. doi:10.1158/1538-7445.AM2015-5307
T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses (2011)

Reactions to pathogens are usually tuned to effect immunity and limit tissue damage. Several host counterinflammatory mechanisms inhibit tissue damage but these may also act to constrain the effectiveness of immunity to acute infections, as we demonstrate in mice acutely infected with influenza A virus (IAV). We show that compared with wild type (WT), galectin-9 knockout (G9KO) mice mounted a more robust acute phase virus-specific CD8 T-cell response as well as higher and more rapid virus-specific serum IgM, IgG, and IgA responses and also cleared virus more rapidly than did WT mice. Blocking galectin-9 signals to Tim-3-expressing cells using a Tim-3 fusion protein resulted in improved immune responses in WT mice. When IAV immune mice were challenged with a heterologous IAV, the secondary IAV-specific CD8 T-cell responses were four- to fivefold higher in G9KO compared with WT mice. Our results indicate that manipulating galectin signals may represent a convenient approach to improve immune responses to some vaccines.
Applications of Augmented Reality in Orthopaedic Spine Surgery (2023)

The application of augmented reality (AR) in surgical settings has primarily been as a navigation tool in the operating room because of its ease of use and minimal effect on surgical procedures. The surgeon can directly face the surgical field while viewing 3D anatomy virtually, thus reducing the need to look at an external display, such as a navigation system. Applications of AR are being explored in spine surgery. The basic principles of AR include data preparation, registration, tracking, and visualization. Current literature provides sufficient preclinical and clinical data evidence for the use of AR technology in spine surgery. AR systems are efficient assistive devices, providing greater accuracy for insertion points, more comfort for surgeons, and reduced operating time. AR technology also has beneficial applications in surgical training, education, and telementorship for spine surgery. However, costs associated with specially designed imaging equipment and physicians' comfort in using this technology continue to remain barriers to its adoption. As this technology evolves to a more widespread use, future applications will be directed by the cost-effectiveness of AR-assisted surgeries.
ChemInform Abstract: ADDITION REACTIONS OF BENZO(B)THIOPHENE. PART 3. ADDITION AND RING‐OPENING REACTIONS WITH PHENOLIC ETHERS (1982)

Abstract Die Ether bzw. Thioether (II) addieren sich in Gegenwart von AlCl 3 an Benzothiophen (I) in irreversibler Reaktion unter Bildung der Produkte (III)+(IV), wobei unerwarteterweise das 2‐Isomere (III) jeweils überwiegt.
Search for long-lived particles using nonprompt jets and missing transverse momentum with proton-proton collisions at s=13TeV (2019)

A search for long-lived particles decaying to displaced, nonprompt jets and missing transverse momentum is presented. The data sample corresponds to an integrated luminosity of 137 fb -1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC in 2016-2018. Candidate signal events containing nonprompt jets are identified using the timing capabilities of the CMS electromagnetic calorimeter. The results of the search are consistent with the background prediction and are interpreted using a gauge-mediated supersymmetry breaking reference model with a gluino next-to-lightest supersymmetric particle. In this model, gluino masses up to 2100, 2500, and 1900 GeV are excluded at 95% confidence level for proper decay lengths of 0.3, 1, and 100 m, respectively. These are the best limits to date for such massive gluinos with proper decay lengths greater than 0.5 m.
The Best Choice of Gasoline/Diesel Particulate Filter to Meet Future Particulate Matter Regulation (2012)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Particulate filter is one of the major technologies to meet air pollution environment regulation since the first introduction to market of diesel passenger car in 2000. It is an indispensable part from September 2011 when the particle number of exhaust gas should be limited for new models. This is also a hot issue for gasoline engines with direct injection technology for improvement of fuel economy even though the EURO 6 regulation for GDI gasoline vehicles is not yet finalized. Car OEMs are under development exploring various options. Otherwise this kind of technology has some task to overcome, such as back pressure resulting in a fuel penalty, burden of increased cost and temperature control within the durable limit. The materials for particulate filters have their own characteristics as material itself. The choice of material is heavily dependent upon the control strategy for soot regeneration. This paper shows what the best selection of particulates filter material is and how to optimize the system for future product competitiveness.&lt;/div&gt;&lt;/div&gt;
Material nanosizing effect on living organisms: non-specific, biointeractive, physical size effects (2009)

Nanosizing effects of materials on biological organisms was investigated by biochemical cell functional tests, cell proliferation and animal implantation testing. The increase in specific surface area causes the enhancement of ionic dissolution and serious toxicity for soluble, stimulative materials. This effect originates solely from materials and enhances the same functions as those in a macroscopic size as a catalyst. There are other effects that become prominent, especially for non-soluble, biocompatible materials such as Ti. Particle size dependence showed the critical size for the transition of behaviour is at approximately 100 microm, 10 microm and 200 nm. This effect has its origin in the biological interaction process between both particles and cells/tissue. Expression of superoxide anions, cytokines tumour necrosis factor-alpha and interleukin-1 beta from neutrophils was increased with the decrease in particle size and especially pronounced below 10 microm, inducing phagocytosis to cells and inflammation of tissue, although inductively coupled plasma chemical analysis showed no dissolution from Ti particles. Below 200 nm, stimulus decreases, then particles invade into the internal body through the respiratory or digestive systems and diffuse inside the body. Although macroscopic hydroxyapatite, which exhibits excellent osteoconductivity, is not replaced with natural bone, nanoapatite composites induce both phagocytosis of composites by osteoclasts and new bone formation by osteoblasts when implanted in bone defects. The progress of this bioreaction results in the conversion of functions to bone substitution. Although macroscopic graphite is non-cell adhesive, carbon nanotubes (CNTs) are cell adhesive. The adsorption of proteins and nano-meshwork structure contribute to the excellent cell adhesion and growth on CNTs. Non-actuation of the immune system except for a few innate immunity processes gives the non-specific nature to the particle bioreaction and restricts reaction to the size-sensitive phagocytosis. Materials larger than cell size, approximately 10 microm, behave inertly, but those smaller become biointeractive and induce the intrinsic functions of living organisms. This bioreaction process causes the conversion of functions such as from biocompatibility to stimulus in Ti-abraded particles, from non-bone substitutional to bone substitutional in nanoapatite and from non-cell adhesive to cell adhesive CNTs. The insensitive nature permits nanoparticles that are less than 200 nm to slip through body defence systems and invade directly into the internal body.
Building efficient wireless sensor networks with low-level naming (2001)

In most distributed systems, naming of nodes for low-level communication leverages topological location (such as node addresses) and is independent of any application. In this paper, we investigate an emerging class of distributed systems where low-level communication does not rely on network topological location. Rather, low-level communication is based on attributes that are external to the network topology and relevant to the application. When combined with dense deployment of nodes, this kind of named data enables in-network processing for data aggregation, collaborative signal processing, and similar problems. These approaches are essential for emerging applications such as sensor networks where resources such as bandwidth and energy are limited. This paper is the first description of the software architecture that supports named data and in-network processing in an operational, multi-application sensor-network. We show that approaches such as in-network aggregation and nested queries can significantly affect network traffic. In one experiment aggregation reduces traffic by up to 42% and nested queries reduce loss rates by 30%. Although aggregation has been previously studied in simulation, this paper demonstrates nested queries as another form of in-network processing, and it presents the first evaluation of these approaches over an operational testbed.
Formation and growth of contact nuclei (1981)

Contact nucleation in the citric acid monohydrate-water system was studied using a photomicroscopic technique. The (100) face of a parent crystal of citric acid monohydrate was contacted by sliding along a glass plate. When the parent crystal was contacted while in saturated solution, no nuclei were formed; however, nuclei were formed when the parent crystal was contacted in supersaturated solution. These results suggest that a growing crystal surface is necessary for formation of the nuclei and that breakage of the parent is not the source of the nuclei;The growth rates and size distribution of the nuclei formed were determined from photographs taken at timed intervals. The growth rate of any individual crystal was found to be invariant with time, but the growth rate from crystal to crystal varied indicating growth rate dispersion. The growth rates of the nuclei were found to be correlated to initial size and to supercooling; however, the dependence on initial size was not strong;Estimates for the parameters of gamma distributions were determined from the initial size and growth rate data. The distributions described with these parameters were used in a model which predicts the presence of large numbers of crystals at small sizes that cause curvature in the semilogarithmic population density-size plot from a MSMPR crystallizer. This curvature had been generally attributed to size dependent growth rates, but the present work indicates that growth rate dispersion is the primary source of the curvature. The inclusion of growth rate dependence on initial size had little effect on the results, indicating that this dependence can be neglected. Finally, the width of the initial size distribution had a negligible effect on the product crystal size distribution (CSD), while the width of the growth rate distribution had a profound effect. The semilogarithmic population density-size plot was found to curve more for wider growth rate distributions, further demonstrating the significance of growth rate dispersion on the product CSD.
Assessment of Uncertainty in Saturation Estimated from Archie's Equation (2009)

Abstract Volumetric methods are used to estimate the hydrocarbons in place of a reservoir. They require petrophysical data including porosity φ and water saturation Sw which can not be directly measured but must be inferred from other measurements. For example, water saturation is conventionally obtained from the Archie's equation, which requires inputs of porosity, ø, cementation factor, m, tortuosity factor, a, saturation exponent, n, true reservoir resistivity, Rt, and resistivity of formation water, Rw. Uncertainties in these input values directly affect the accuracy of water saturation estimation. In this paper, we investigate the propagation of uncertainties of these input parameters into Sw estimated by Archie's equation. Error propagation equations (based on a Taylor series expansion of Sw around the mean values of the input paramaters) are derived for uncertainty characterization. Two cases are considered for the relationship between the input parameters; correlated or completely independent. It is shown that correlation among the input parameters, which may be due to different rock facies, can increase or decrease uncertainty in Sw and hence, ignoring existing correlation among the input parameters may lead to incorrectly characterizing the uncertainty in Sw. In addition, the dimensionless sensitivities and relative uncertainties of the input parameters, derived from the error propagation equations, clearly identify which of the input parameters will dominate the total uncertainty in Sw computations. Monte Carlo methods were used to verify the developed error propagation equations. A comparative study shows that the error propagation method is a good first approximation for uncertainty analysis, especially if the resulting Sw distributions are normal. However, it is well known that Monte Carlo methods are more general as they provide rigorous sampling of the response function (Sw in our problem) by accounting for the nonlinearity existing between the response function and its input parameters, and thus should be used for accurately quantifying the uncertainty.
Truncate-and-Forward: A New Coding Strategy for the General Relay Channel (2006)

In this work we focus on the general relay channel. We present a new coding strategy that yields a rate increase over the point-to-point rate for any channel conditions without the use of auxiliary random variables. Specifically, even when Cover &amp;amp; El-Gamal’s decode-and-forward or estimate-and-forward strategies do not exceed the point-to-point rate, our method results in a rate to the destination that is greater than that rate. We then consider the cooperative broadcast scenario with a single common message and show how the new relaying strategy can be used to derive a multi-step conference that achieves the full cooperation rate bound for conference capacities which are less than the Slepian-Wolf condition. This simple method can be extended to other network scenarios to improve results for the case where the relay is very noisy.
Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of α-tubulin acetylation and FGF-21 up-regulation (2016)

Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as α-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction, and ameliorated neuronal cell death in MCAO rats. These beneficial effects lasted at least three days after MCAO. Notably, when given at 24 hours after MCAO, TubA still exhibited significant protection. Levels of acetylated α-tubulin were decreased in the ischemic hemisphere on Days 1 and 3 after MCAO, and were significantly restored by TubA. MCAO markedly downregulated fibroblast growth factor-21 (FGF-21) and TubA significantly reversed this downregulation. TubA also mitigated impaired FGF-21 signaling in the ischemic hemisphere, including up-regulating β-Klotho, and activating ERK and Akt/GSK-3β signaling pathways. In addition, both TubA and exogenous FGF-21 conferred neuroprotection and restored mitochondrial trafficking in rat cortical neurons against glutamate-induced excitotoxicity. Our findings suggest that the neuroprotective effects of TubA likely involve HDAC6 inhibition and the subsequent up-regulation of acetylated α-tubulin and FGF-21.
Association of colorectal cancer intrinsic subtypes with prognosis, chemotherapy response, deficient mismatch repair, and epithelial to mesenchymal transition (EMT). (2013)

3530 Background: Unbiased genome-wide analyses of gene expression patterns have been successfully used for molecular classification of breast cancer into subtypes that have clear relevance for prognosis and treatment. A similar classification is still missing for colorectal cancer (CRC). Methods: Using full genome expression data of 188 stage I-IV CRC patients, an unsupervised clustering revealed three major subtypes (A-, B-, C-type). A molecular subtype classification was developed and validated in 543 stage II and III patients. The subtypes were analyzed for correlation to clinical information, mutations in the kinome, known molecular markers status and chemotherapy response. In addition, subtypes were determined on 173 samples from The Cancer Genome Atlas (TCGA) colon dataset with Agilent genome expression data. Results: C-type patients have the worst outcome, a mesenchymal phenotype, and show no benefit from adjuvant chemotherapy treatment. Patients having A- or B-type tumors have a better clinical outcome, a more proliferative and epithelial phenotype and benefit from adjuvant chemotherapy. A- and C-type groups are enriched for tumors having oncogenic BRAF mutations and a deficient DNA mismatch repair system. B-type tumors showed a low overall kinome mutation frequency (1.6%), while both A- and C-type patients harbor a higher mutation frequency (respectively 4.2 and 6.2%), in agreement with their mismatch repair deficiency. Finally, CRC subtyping was confirmed in the colon TCGA dataset with 26 samples classified as A-type, 110 as B-type and 37 as C-type. In agreement with the different aggressiveness of the subtypes, A-type tumors were less prevalent in stage IV while C-type were less prevalent in stage I CRC. Conclusions: The heterogeneity of the intrinsic subtypes is largely based on three biological hallmarks of the tumor: an epithelial-to-mesenchymal transition, deficiency in mismatch repair genes that result in a high mutation frequency associated with MSI, and cellular proliferation. These subtypes are clinically relevant, as they differ in their underlying biology and might require different treatment strategies.