gebhart/patrepeval huggingface dataset:
Connexin‐purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation (2017)

Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance, limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut, predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (<i>in vivo</i>) but not upon direct exposure of glia to morphine (<i>in vitro</i>). LPS, a major bacterial product, also increased ATP-induced currents, as well as expression of P2X4, P2X7, IL6, IL-1β mRNA in enteric glia. LPS increased connexin43 (Cx43) expression and enhanced ATP release from enteric glia cells. LPS-induced P2X currents and proinflammatory cytokine mRNA expression were blocked by the Cx43 blockers Gap26 and carbenoxolone. Likewise, colonic inflammation related to prolonged exposure to morphine was significantly attenuated by carbenoxolone (25 mg/kg). Carbenoxolone also prevented gut wall disruption and significantly reduced morphine-induced constipation. These findings imply that enteric glia activation is a significant modulator of morphine-related inflammation and constipation.-Bhave, S., Gade, A., Kang, M., Hauser, K. F., Dewey, W. L., Akbarali, H. I. Connexin-purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation.
Isolating Features of Object and Its State for Compositional Zero-Shot Learning (2023)

The purpose of Compositional Zero Shot Learning (CZSL) is to recognize previously unseen compositions of known objects (e.g. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">apple, banana</i> ) and their states (e.g. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ripe, unripe</i> ) as seen in an image. The CZSL is a challenging problem as it is difficult to isolate the visual features of object and its states from its compositions in images. The features of a state may have wide variation across different compositions. For example, the state <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sliced</i> has different visual features in compositions <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sliced apple</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sliced tomato</i> . In this paper, we attempt to solve the problem of CZSL using a two-stage recognition approach. Each stage sequentially performs recognition task utilising two distinct modalities of compositions. The modalities are image features as well as textual features representing features of objects and states respectively. We propose a novel gradient regularized loss term for better disentanglement of object and state features from the visual features of the composition. An appropriate disentanglement of the features of visual primitives (states and objects) leads to correct identification of images of unseen state-object compositions. The proposed approach and the competing methods are evaluated on three benchmark datasets, MIT States, UT-Zappos50 k and CGQA. Our extensive experiments establish the efficacy of our proposed algorithm that outperforms other state-of-the-art approaches.
Abstract A39: Viral response markers in immune-competent solid tumors by immunohistochemistry (2018)

Abstract Background: Immune checkpoint blockade remarkably provides durable clinical response in solid tumors and immunohistochemistry (IHC) measures are current companion diagnostics. Currently four (4) IHC companion diagnostics of Programed Death Ligand (PD-L1) are components of FDA approved clinical trials. The marked clinical responses seen in checkpoint inhibition outpace basic science advances. Our previous reports of interferon mediated viral response against dsRNA intermediates, namely in colon and bladder cancer, have examined the role of global demethylation (5-AZA) and combination therapies. Materials and Methods: Cell lines HCT116 (colon) and T24 (bladder) were treated with single and combination therapy of 5-AZA and Vitamin C were formalin fixed and processed for IHC staining for Ki67, MHL1 and markers of viral response: dsRNA markers (K1, J2), interferon activation (RIG I, MDA5, IFIT1, IFI27, IRF7, IRF9, and pSTAT1. Immune related markers included CD4, CD8, CD68, CD163 and PD-L1 (clone SP263). TMA sections were stained by automated immunostainers to include a subset of patient-matched whole sections. IHC staining documented for protein abundance (intensity 0-3) and cellular localization (nuclear, cytoplasmic, membranous) Results: Colon cell line experiments confirmed viral response activation with correlative staining of dsRNA antibodies with viral response markers RIG1, MDA5, IFIT1, IFI27, IRF7 and pSTAT1 with robust staining in formalin fixed paraffin embedded (FFPE) tissues with the exception of IFI27 and RIG1. Immune and macrophage markers CD8, CD4, CD68, and CD163 showed variable correlation with viral response markers and PD-L1 staining heterogeneous and most prevalent in non-small cell lung cancer (34%). Of 3 MMR deficient colon cancers, 2 stained positive for PD-L1. MDA5 staining was present in tumor and stroma but stronger peri-tumoral suggesting relation to tumor infiltrating lymphocytes. TMA cores and corresponding whole sections with co-expressed PD-L1 and MDA5 showed marked diminished CD8 staining as verified by nuclear quantitative algorithm. Summary: Here we evaluate the viral response phenotype via global demethylation in solid tumors with emphasis on colon and bladder cancer. lung and breast cancer. IHC methods in cell lines and FFPE clinical tissues provide a robust strategy to link viral and immune response in clinical tissue samples and provides glimpses of viral and immune pathways that might better elucidate tumor biology and thereby predict tumor response to drug regimens that include checkpoint inhibitors. Citation Format: Galen Hostetter, Liu Minmin, Marie Mustert, Bree Berghuis, Lisa Turner, Peter Jones, Steve Baylin, Scott Jewell, Lorenzo Sempere. Viral response markers in immune-competent solid tumors by immunohistochemistry [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A39.
Erythropoietin Promotes Erection Recovery After Nerve-Sparing Radical Retropubic Prostatectomy: A Retrospective Analysis (2008)

Erythropoietin administration on the preoperative day before undergoing nerve-sparing radical prostatectomy in men reporting normal erectile function preoperatively may confer improved erectile function recovery postoperatively.
Cytotoxic α-Pyrones from Xylaria hypoxylon (2007)

Two new alpha-pyrone derivatives, xylarone (1) and 8,9-dehydroxylarone (2) possessing cytotoxic activities, were isolated from the culture fluid of submerged cultures of the ascomycete Xylaria hypoxylon, strain A27-94. Their structures were elucidated by spectroscopic methods.
Use of pressure mapping for quantitative analysis of pressure points induced by external coaptation of the distal portion of the pelvic limb of dogs (2018)

OBJECTIVE To quantitatively measure the amount of pressure induced at the calcaneus and cranial tibial surface of dogs by use of 2 cast configurations. ANIMALS 13 client- or student-owned dogs. PROCEDURES Pressure sensors were placed over the calcaneus and cranial tibial surface. Dogs then were fitted with a fiberglass cast on a pelvic limb extending from the digits to the stifle joint (tall cast). Pressure induced over the calcaneus and proximal edge of the cast at the level of the cranial tibial surface was simultaneously recorded during ambulation. Subsequently, the cast was shortened to end immediately proximal to the calcaneus (short cast), and data acquisition was repeated. Pressure at the level of the calcaneus and cranial tibial surface for both cast configurations was compared by use of paired t tests. RESULTS The short cast created significantly greater peak pressure at the level of the calcaneus (mean ± SD, 0.2 ± 0.07 MPa), compared with peak pressure created by the tall cast (0.1 ± 0.06 MPa). Mean pressure at the proximal cranial edge of the cast was significantly greater for the short cast (0.2 ± 0.06 MPa) than for the tall cast (0.04 ± 0.03 MPa). CONCLUSIONS AND CLINICAL RELEVANCE A cast extended to the level of the proximal portion of the tibia caused less pressure at the level of the calcaneus and the proximal cranial edge of the cast. Reducing the amount of pressure at these locations may minimize the potential for pressure sores and other soft tissue injuries.
Adaptive mapping to resource availability for dynamic wavelet-based applications (2007)

Platforms have to cope with unpredictably varying system resource requirements, because of inter-task level dynamism. To deal with this, they have to be at least partially reconfigurable. It is then important for applications to optimally exploit the memory hierarchy under varying memory availability. Moreover, in the case of intra-task dynamism, additional unpredictability is inserted and the exploration of the optimal memory hierarchy depends on data dependent application behavior. This paper presents a mapping strategy for a wavelet-based video application: depending on the encountered resource availability, switching to different memory optimized instantiations (i.e. localizations) of the application offers up to 25% energy gains in memory accesses, for a representative test sequence. We observe that it is possible to exploit the input motion characteristics in detail (that reflect the intra-task dynamism) by enabling motion-triggered switching, and further increase the achieved gains.
Genetics of Type 1 Diabetes: Similarities and Differences between Asian and Caucasian Populations (2006)

Abstract: Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. We therefore studied the association of candidate genes, HLA, INS, CTLA4, PTPN22, and SUMO4 , with type 1 diabetes in Asian populations in comparison with Caucasian populations. Class II HLA was strongly associated with type 1 diabetes in both Asian and Caucasian populations, but alleles associated with type 1 diabetes are different among different ethnic groups due to difference in allele distribution in general populations. INS was associated with type 1 diabetes in both Japanese and Caucasian populations, but frequency of disease‐associated haplotype was markedly higher in Japanese than in Caucasian populations. CTLA4 association was reported for both type 1 diabetes and autoimmune thyroid diseases (AITD) in Caucasian populations, but the association with type 1 diabetes was concentrated in a subset of patients with AITD in Japanese. A variant (R620W) of PTPN22 was consistently associated with type 1 diabetes in Caucasian populations, but the variant was absent in Asian populations including Japanese. M55V variant of SUMO4 was significantly associated with type 1 diabetes in Asians, but genetic heterogeneity between Asian and Caucasian populations was suggested. These data indicate the importance of transracial studies with a large number of samples in each ethnic group in genetic dissection of type 1 diabetes.
In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572 (2010)

In this study of nine clinical isolates obtained from integrase inhibitor-naïve HIV-2-infected patients, the median EC₅₀ value for the new integrase inhibitor S/GSK1349572 was 0.8 nM (range 0.2-1.4), and is similar to HIV-1 reference strains. We found a seven-, 13- and 18-fold increase in EC₅₀ values to S/GSK1349572 for the HIV-2 double (T97A + Y143C; G140S + Q148R) and triple (G140T + Q148R + N155H) mutants, respectively, obtained from two raltegravir-experienced patients.
Exploration of electrical impedance spectroscopy for monitoring bone healing: a pilot study in rabbits (2020)

In 2019, Lin et al. published a proof-of-concept study of electrical impedance spectroscopy as a simple and low-cost method to characterize progression of fracture repair (Lin et al., Sci Rep 2019). However, the electrical impedance sensors were placed in the fracture site which may impair the transfer to clinical use. To further explore the concept of monitoring fracture healing by electrical impedance spectroscopy, we established a tibial fracture model in the rabbit where sensors are positioned in proximity to the fracture site but without being placed in the fracture site. The aim of this pilot study was to explore whether distinct patterns of electrical impedance would evolve as tibial fractures in rabbits were evaluated until radiographic signs of healing. Approval was granted from the Inspectorate of the Animal Experimentation under the Danish Ministry of Justice. Four rabbits were anaesthetized, and in each rabbit a tibial osteotomy was made and stabilized by an external fixator. Electrical impedance was measured immediately postoperative and hereafter daily until euthanization after 3 weeks. Recordings were obtained within a wide frequency range (10 Hz to 1 MHz) from an inner electrode placed into the medullary canal and an outer electrode placed extracortical on the lateral with a distance of 3 mm to the defect. A similar pattern of electrical impedance over time was observed in the four rabbits. During the very early stages of fracture healing, an initial fluctuation in electrical impedance occurred. However, after 10 days the curves revealed a steady daily increase in electrical impedance. The first radiological signs of bone healing were detected after 14 days and progressed in all four rabbits in accordance with increments in the electrical impedance until termination of the pilot study after 21 days. Consistent electrical impedance patterns were detected during bone healing in a pilot study of four rabbits. Further research is needed to explore whether the presented method of electrical impedance measurements can be used to monitor bone healing over time.
O-159 Is Blastocyst ET Better Than Day 3-ET With Assisted Hatching in the (2000)

Blastocyst (B) 32 36.3 14.7* 9.8* 6.5* 1.6 15 (46.8%) 12 (37.5%) Day 3 (D3) 45 36.2 10.5 4.9 5.3 4.3 18 (40%) 17 (37.8%) * p,0.5 vs. D3.
Microbial Synthesis of Human-Hormone Melatonin at Gram Scales (2020)

Melatonin is a commercially attractive tryptophan-derived hormone. Here we describe a bioprocess for the production of melatonin using <i>Escherichia coli</i> to high titers. The first engineered strain produced 0.13 g/L of melatonin from tryptophan under fed-batch fermentation conditions. A 4-fold improvement on melatonin titer was further achieved by (1) protein engineering of rate-limiting tryptophan hydroxylase to improve 5-hydroxytryptophan biosynthesis and (2) chromosomal integration of aromatic-amino-acid decarboxylase to limit byproduct formation and to minimize gene toxicity to the host cell. Fermentation optimization improved melatonin titer by an additional 2-fold. Deletion of <i>yddG</i>, a tryptophan exporter, exhibited an additive beneficial effect. The final engineered strain produced ∼2.0 g/L of melatonin with tryptophan supplemented externally and ∼1.0 g/L with glucose as the sole carbon source for tryptophan supply. This study lays the foundation for further developing a commercial melatonin-producing <i>E. coli</i> strain.
Cytocompatibility of Ti3AlC2, Ti3SiC2, and Ti2AlN: In Vitro Tests and First-Principles Calculations (2017)

Herein, the cytocompatibility of selected MAX phases, Ti<sub>3</sub>AlC<sub>2</sub>, Ti<sub>3</sub>SiC<sub>2</sub>, and Ti<sub>2</sub>AlN, were systematically evaluated using <i>in vitro</i> tests for the first time. These phases were anoxic to preosteoblasts and fibroblasts. Compared with the strong viable fibroblasts, the different cellular responses of these materials were clearly distinguishable for the preosteoblasts. Under an osteoblastic environment, Ti<sub>2</sub>AlN exhibited better cell proliferation and differentiation performance than Ti<sub>3</sub>AlC<sub>2</sub> and Ti<sub>3</sub>SiC<sub>2</sub>. Moreover, the performance was superior to that of a commercial Ti-6Al-4V alloy and comparable to that of pure Ti. A possible mechanism was suggested based on the different surface oxidation products, which were determined from the binding energy of adsorbed Ca<sup>2+</sup> ions using first-principles calculations. Compared with the partially oxidized TiC<sub><i>x</i></sub>O<sub><i>y</i></sub> layer on Ti<sub>3</sub>AlC<sub>2</sub> and Ti<sub>3</sub>SiC<sub>2</sub>, the partially oxidized TiN<sub><i>x</i></sub>O<sub><i>y</i></sub> layer on the Ti<sub>2</sub>AlN had a stronger affinity to the Ca<sup>2+</sup> ions, which indicated the good cytocompatibility of Ti<sub>2</sub>AlN.
What Can an Organ-on-a-Chip Teach Us About Human Lung Pathophysiology? (2022)

The intertwined relationship between structure and function has been key to understanding human organ physiology and disease pathogenesis. An organ-on-a-chip (organ chip) is a bioengineered microfluidic cell culture device lined by living cells and tissues that recapitulates organ-level functions in vitro. This is accomplished by recreating organ-specific tissue-tissue interfaces and microenvironmental biochemical and mechanical cues while providing dynamic perfusion through endothelium-lined vascular channels. In this review, we discuss how this emerging technology has contributed to the understanding of human lung structure-function relationships at the cell, tissue, and organ levels.
Targeted inhibition of human hematological cancers in vivo by doxorubicin encapsulated in smart lipoic acid-crosslinked hyaluronic acid nanoparticles (2017)

The chemotherapy of hematological cancers is challenged by its poor selectivity that leads to low therapeutic efficacy and pronounced adverse effects. Here, we report that doxorubicin encapsulated in lipoic acid-crosslinked hyaluronic acid nanoparticles (LACHA-DOX) mediate highly efficacious and targeted inhibition of human hematological cancers including LP-1 human multiple myeloma (MM) and AML-2 human acute myeloid leukemia xenografted in nude mice. LACHA-DOX had a size of ca. 183 nm and a DOX loading content of ca. 12.0 wt.%. MTT and flow cytometry assays showed that LACHA-DOX possessed a high targetability and antitumor activity toward CD44 receptor overexpressing LP-1 human MM cells and AML-2 human acute myeloid leukemia cells. The in vivo and ex vivo images revealed that LACHA-DOX achieved a significantly enhanced accumulation in LP-1 and AML-2 tumor xenografts. Notably, LACHA-DOX effectively suppressed LP-1 as well as AML-2 tumor growth and drastically increased mice survival rate as compared to control groups receiving free DOX or PBS. Histological analyses exhibited that LACHA-DOX caused little damage to the major organs like liver and heart. This study provides a proof-of-concept that lipoic acid-crosslinked hyaluronic acid nanoparticulate drugs may offer a more safe and effective treatment modality for CD44 positive hematological malignancies.
Capsules with Inverted Dot-Product Attention Routing (2020)

We introduce a new routing algorithm for capsule networks, in which a child capsule is routed to a parent based only on agreement between the parent's state and the child's vote. The new mechanism 1) designs routing via inverted dot-product attention; 2) imposes Layer Normalization as normalization; and 3) replaces sequential iterative routing with concurrent iterative routing. When compared to previously proposed routing algorithms, our method improves performance on benchmark datasets such as CIFAR-10 and CIFAR-100, and it performs at-par with a powerful CNN (ResNet-18) with 4x fewer parameters. On a different task of recognizing digits from overlayed digit images, the proposed capsule model performs favorably against CNNs given the same number of layers and neurons per layer. We believe that our work raises the possibility of applying capsule networks to complex real-world tasks. Our code is publicly available at: https://github.com/apple/ml-capsules-inverted-attention-routing An alternative implementation is available at: https://github.com/yaohungt/Capsules-Inverted-Attention-Routing/blob/master/README.md
Current and Future Treatments for Diabetic Retinopathy (2022)

The pathogenesis of diabetic retinopathy in humans remains imperfectly understood; in particular, the kinetics of the various pathogenic events in the very early stages of retinal damage are difficult to recognize [...].
Templated Synthesis of Carbon Materials from Zeolites (Y, Beta, and ZSM-5) and a Montmorillonite Clay (K10):  Physical and Electrochemical Characterization (2001)

New high surface area carbon materials were prepared at low temperature (600 °C) using zeolite (Y, Beta, and ZSM-5) and montmorillonite clay (K10) templates. Acrylonitrile, furfuryl alcohol, pyrene, and vinyl acetate precursors were polymerized and carbonized in each of the inorganic matrixes without the addition of a polymerizing agent. The templates were removed by acid demineralization and the resulting carbon materials were physically characterized by infrared spectroscopy, BET (N2) surface area analysis, energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), and elemental analyses. Electrochemical characterizations were also conducted. Cyclic voltammetry was employed to examine the synthesized carbons in the oxidation of catechol to hydroquinone and quinone, a model reaction that is known to be surface dependent. The identities of both the template and the substrate affected the electrochemical response. Additionally, the ability of the new carbons to intercalate and deintercalate lithium was investigated. While all of the synthesized carbons displayed high irreversible capacities consistent with other low-temperature carbons, the carbons prepared from zeolite Y displayed unique voltage curves, suggesting template effects on the carbon. In addition, all of the carbons prepared for this study displayed significant voltage hysteresis on charge/discharge.
Use of the polymerase chain reaction for Salmonella detection (1996)

A primer set of oligonucleotides (S18 and S19) from the ompC gene of Salmonella has been evaluated for specific detection of Salmonella by polymerase chain reaction (PCR). This primer set successfully amplified 40 Salmonella serovars (60 isolates), but not 24 non-Salmonella bacteria (42 isolates) that have been tested so far. The uniqueness of these primer sequences was also confirmed. The sensitivity of PCR detection in extracted chromosomal DNA for Salm. typhimurium was 1 pg. The sensitivity for boiled whole bacteria was 400 cells. The detection of Salm. typhimurium in ground beef samples required 4-6 h enrichment with an initial inocula of 100 bacteria.