gebhart/patrepeval huggingface dataset:
Complications of scaphoid silicone arthroplasty. (1985)

Between 1971 and 1982, thirty-three patients underwent scaphoid silicone arthroplasty, and twenty-three of them were available for review after an average of three years of follow-up. Radiographically, there was evidence of carpal collapse with a progressive decrease in carpal height and a progressive increase in the scapholunate angle in thirteen wrists. Subluxation of the spacer occurred in thirteen patients, and nine of them also had dislocation of the trapezial stem. Clinically, grip strength did not improve and wrist motion increased only slightly. There were complaints of pain associated with subluxation of the spacer in more than half of the patients. Ten patients, eight of whom had a subluxated spacer, underwent thirteen secondary surgical procedures.
Role of bacterial infections in allograft rejection (2008)

Advances in immunosuppressive strategies have been essential for organ transplantation becoming an established therapy for the treatment of end-stage organ failure. A global state of immunosuppression imparted by current regimens leaves the transplant recipient at a significantly increased risk for a multitude of infections. As such, recognition, prevention and treatment of infection have become primary concerns. Furthermore, as our understanding of the interaction between the innate and adaptive immune system expands, the potential for enhanced alloreactivity in the face of infection has become a topic of increasing interest. Recent studies have shown a correlation between viral infections and graft rejection. However, other categories of infection, including bacterial infections, have the potential to elicit similar immune responses. This review seeks to explore the clinical and scientific literature examining the role of bacterial infections in transplant rejection.
Sex Differences in Retinal Microvasculature Through Puberty In Type 1 Diabetes: Are Girls at Greater Risk of Diabetic Microvascular Complications? (2014)

This is the first longitudinal study to repeatedly examine RVG through puberty in youth with T1D. Sex dimorphism was observed. Female sex was associated with lower LDRa, wider venules, and earlier onset of retinopathy. These RVG patterns have been associated with incident microvascular complications but did not reach statistical significance in this study. Larger studies are needed to investigate the RVG, microvascular complications, and sex associations early in the course of T1D.
Overcoming gefitinib resistance in NSCLC via inactivation of the PI3K/AKT signaling pathway by a combination of FUS1 nanoparticles and EGFR inhibitors. (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Gefitinib (Iressa) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been shown to be clinically effective in a subpopulation of non small cell lung cancer (NSCLC) patients. Despite initial responses to gefitinib in some NSCLC patients, cancer eventually progresses by unknown mechanisms of acquired resistance. We explored the use of the novel tumor suppressor FUS1 to enhance the chemotherapeutic potency of gefitinib and overcome gefitinib resistance in NSCLC. We found that reactivation of wild-type FUS1 by FUS1 nanoparticle-mediated gene transfer into FUS1-deficient and gefitinib-resistant NSCLC H1299, H322, H358, and H460 cells significantly ( P < 0.001) sensitized their response to gefitinib treatment and synergistically induced apoptosis in vitro and in an H322 orthotopic lung cancer mouse model. To understand the mechanism of gefitinib-induced resistance, we established a gefitinib-resistant HCC827GR NSCLC cell line (IC50 = 16 μM) by selecting against gefitinib from the parental HCC827 cells that contain an activating deletion mutation of the EGFR gene and are extremely sensitive to gefitinib treatment (IC50 = 0.016 μM). We found no secondary mutations in the EGFR gene in the HCC827GR cells, but these cells registered a significantly elevated level of phosphorylated AKT protein. Combination treatment with FUS1 nanoparticles and gefitinib at a dose level of IC10 significantly re-sensitized the cells to gefitinib, as demonstrated by synergistically enhanced growth inhibition and apoptosis. FUS1 nanoparticle treatment alone or with gefitinib markedly inactivated EGFR and AKT, as demonstrated by decreased phosphorylation levels of both proteins on Western blots, compared with either agent alone. Cleavage of caspase-3, caspase-9, and PARP was also significantly induced by the combination of FUS1 and gefitinib in HCC872GR and other gefitinib-resistant NSCLC cells. Our results suggest that a combination treatment of FUS1 nanoparticles and gefitinib could overcome drug-induced resistance by simultaneously inactivating EGFR and the AKT signaling pathway and by facilitating apoptosis. This abstract is supported by grants from NCI (SPORE P50CA70907) and DOD (TARGET, DAMD17002-1-0706).
Low complexity low power non-recursive digital filters with unconstrained topology (2011)

Current methods used to design multiplierless digital filter have demonstrated their potential to construct low complexity circuits from multiplier blocks with few adders in order to replace the multipliers of standard Finite Impulse Response structures. However, the traditional approach only provides a local optimization as it need to rely to defined circuit architectures, such as the direct form structure. This paper presents a population-based metaheuristic that constructs multiplierless non-recursive filters without referring to any circuit topology. Simulations demonstrate that our algorithm is able to design typical digital filters, such as low-pass and high-pass filters, that can be used in communication systems and that need a significantly reduced amount of power to process the signal.
Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy (2020)

Fluence rate is an effector of photodynamic therapy (PDT) outcome. Lower light fluence rates can conserve tumor perfusion during some illumination protocols for PDT, but then treatment times are proportionally longer to deliver equivalent fluence. Likewise, higher fluence rates can shorten treatment time but may compromise treatment efficacy by inducing blood flow stasis during illumination. We developed blood-flow-informed PDT (BFI-PDT) to balance these effects. BFI-PDT uses real-time noninvasive monitoring of tumor blood flow to inform selection of irradiance, i.e., incident fluence rate, on the treated surface. BFI-PDT thus aims to conserve tumor perfusion during PDT while minimizing treatment time. Pre-clinical studies in murine tumors of radiation-induced fibrosarcoma (RIF) and a mesothelioma cell line (AB12) show that BFI-PDT preserves tumor blood flow during illumination better than standard PDT with continuous light delivery at high irradiance. Compared to standard high irradiance PDT, BFI-PDT maintains better tumor oxygenation during illumination and increases direct tumor cell kill in a manner consistent with known oxygen dependencies in PDT-mediated cytotoxicity. BFI-PDT promotes vascular shutdown after PDT, thereby depriving remaining tumor cells of oxygen and nutrients. Collectively, these benefits of BFI-PDT produce a significantly better therapeutic outcome than standard high irradiance PDT. Moreover, BFI-PDT requires ~40% less time on average to achieve outcomes that are modestly better than those with standard low irradiance treatment. This contribution introduces BFI-PDT as a platform for personalized light delivery in PDT, documents the design of a clinically-relevant instrument, and establishes the benefits of BFI-PDT with respect to treatment outcome and duration.
Parallelized Hashing via &lt;i&gt;j&lt;/i&gt;-Lanes and &lt;i&gt;j&lt;/i&gt;-Pointers Tree Modes, with Applications to SHA-256 (2014)

j-lanes tree hashing is a tree mode that splits an input message into j slices, computes j independent digests of each slice, and outputs the hash value of their concatenation. j-pointers tree hashing is a similar tree mode that receives, as input, j pointers to j messages (or slices of a single message), computes their digests and outputs the hash value of their concatenation. Such modes expose parallelization opportunities in a hashing process that is otherwise serial by nature. As a result, they have a performance advantage on modern processor architectures. This paper provides precise specifications for these hashing modes, proposes appropriate IVs, and demonstrates their performance on the latest processors. Our hope is that it would be useful for standardization of these modes.
Ultra-thin, reconfigurable meta-optics using optical phase change materials (Conference Presentation) (2018)

The dramatic optical property change of optical phase change materials (O-PCMs) between their amorphous and crystalline states potentially allows the realization of reconfigurable photonic devices with enhanced optical functionalities and low power consumption, such as reconfigurable optical components, optical switches and routers, and photonic memories. Conventional O-PCMs exhibit considerable optical losses, limiting their optical performance as well as application space. In this talk, we present the development of a new group of O-PCMs and their implementations in novel meta-optic devices. Ge-Sb-Se-Te (GSST), obtained by partially substituting Te with Se in traditional GST alloys, feature unprecedented broadband optical transparency covering the telecommunication bands to the LWIR. A drastic refractive index change between the amorphous and crystalline states of GSST is realized and the transition is non-volatile and reversible. Optical metasurfaces consist of optically-thin, subwavelength meta-atom arrays which allow arbitrary manipulation of the wavefront of light. Capitalizing on the dramatically-enhanced optical performance of GSST, transparent and ultra-thin reconfigurable meta-optics in mid-infrared are demonstrated. In one example, GSST-based all-dielectric nano-antennae are used as the fundamental building blocks for meta-optic components. Tunable and switchable metasurface devices are developed, taking advantage of the materials phase changing properties.
Rapid quantitative T2 mapping of the prostate using three‐dimensional dual echo steady state MRI at 3T (2016)

Rapid 3D T<sub>2</sub> mapping in the entire prostate can be performed in 1 min using DESS MRI. Magn Reson Med 76:1720-1729, 2016. © 2016 International Society for Magnetic Resonance in Medicine.
Observation of an anomalously large blueshift of apparent donor–acceptor pair transition peak in compensation-doped quantum wells (1998)

We have observed an anomalously large blueshift of the apparent donor–acceptor pair transition peak as the laser intensity increases in compensation-doped coupled quantum wells. The mechanism for the blueshift is the change of the Coulomb interaction energy between the recombined donors and acceptors due to the decrease in their separation as the laser intensity increases. The blueshift is accompanied by the saturation of the relative donor–acceptor pair transition peak intensity due to filling of the impurity states.
Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface (2022)

Influenza virus hemagglutinin (HA) has been the primary target for influenza vaccine development. Broadly protective antibodies targeting conserved regions of the HA unlock the possibility of generating universal influenza immunity. Two group 2 influenza A chimeric HAs, cH4/3 and cH15/3, were previously designed to elicit antibodies to the conserved HA stem. Here, we show by X-ray crystallography and negative-stain electron microscopy that a broadly protective antistem antibody can stably bind to cH4/3 and cH15/3 HAs, thereby validating their potential as universal vaccine immunogens. Furthermore, flexibility was observed in the head domain of the chimeric HA structures, suggesting that antibodies could also potentially interact with the head interface epitope. Our structural and binding studies demonstrated that a broadly protective antihead trimeric interface antibody could indeed target the more open head domain of the cH15/3 HA trimer. Thus, in addition to inducing broadly protective antibodies against the conserved HA stem, chimeric HAs may also be able to elicit antibodies against the conserved trimer interface in the HA head domain, thereby increasing the vaccine efficacy.
Discovery of Potent, Selective, and State-Dependent NaV1.7 Inhibitors with Robust Oral Efficacy in Pain Models: Structure–Activity Relationship and Optimization of Chroman and Indane Aryl Sulfonamides (2020)

Voltage-gated sodium channel Na<sub>V</sub>1.7 is a genetically validated target for pain. Identification of Na<sub>V</sub>1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent Na<sub>V</sub>1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over Na<sub>V</sub>1.5, and CYP2C9 inhibition. The lead molecules <b>13</b>, <b>29</b>, <b>32</b>, <b>43</b>, and <b>51</b> showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound <b>51</b> also showed significant effects on the CCI-induced neuropathic pain model. The profile of <b>51</b> indicated that it has the potential for further evaluation as a therapeutic for pain.
In vitro influence of ciprofloxacin on selected functions of rainbow trout (Oncorhynchus mykiss) leucocytes. (2003)

Rhabdoviruses constitute one of the most pathogenic viruses isolated from rainbow trout and carp culture. Several viruses were also isolated from other species of fish. These viruses are mostly associated with epizootics and heavy losses. Spring viraemia of carp virus (SVCV) and pike fry rhabdovirus (PFRV) have been the most extensively studied, due to their significant economic impact. Significant progress has been made towards controlling the major bacterial fish diseases using vaccines, but this approach has not yet been successful in preventing viral diseases in fish culture. However, for an effective therapeutic approach, specific drugs should be developed to selectively inhibit virus replication and/or stimulate antiviral protection. In this investigation we examined the in vitro influence of methisoprinol on the SVCV and virus isolated from catfish (Ictalurus melas) replication by measuring their RNA synthesis. The viruses were propagated in EPC cells and cell cultures containing methisoprinol were followed by infection with SVCV or catfish rhabdovirus suspension containing 10(7) TCID50/ml. Methisoprinol (Polfa, Poland) at concentrations of 0, 100, 200, 300, 400 and 500 microg/ml of medium (Glasgow MEM) was used in this study. The results of this study show the strong inhibition of incorporation (cpm) of [3H]-uridine into SVCV and catfish rhabdovirus RNA in cell culture exposed to methisoprinol at various concentrations. The highest percent of inhibition of viral RNA at 72 h after infection with two rhabdoviruses were observed in doses of 400 and 500 microg/ml of methisoprinol in medium. The results of this in vitro study showed that methisoprinol inhibits the rhabdoviruses isolated from carp and catfish.
Epitope mapping of the neuronal growth inhibitor Nogo‐A for the Nogo receptor and the cognate monoclonal antibody IN‐1 by means of the SPOT technique (2007)

Nogo-A is a potent inhibitor of axonal outgrowth in the central nervous system of adult mammals, where it is expressed as a membrane protein on oligodendrocytes and in myelin. Here we describe an attempt to identify linear peptide epitopes in its sequence that are responsible for the interaction either with the Nogo receptor (NgR) or with the neutralizing monoclonal antibody IN-1. Analysis of an array of immobilized overlapping 15 mer peptides covering the entire amino acid sequence of human Nogo-A (1192 residues) revealed a single epitope with prominent binding activity both towards the recombinant NgR and the IN-1 F(ab) fragment. Further truncation and substitution analysis yielded the minimal epitope sequence 'IKxLRRL' (x not equal to P), which occurs within the so-called Nogo66 region (residues 1054-1120) of Nogo-A. The bacterially produced Nogo66 fragment exhibited binding activity both for the recombinant NgR and for the IN-1 F(ab) fragment on the Western blot as well as in ELISA. Unexpectedly, the synthetic epitope peptide and the recombinant Nogo66 showed cross-reactivity with the 8-18C5 F(ab) fragment, which is directed against myelin oligodendrocyte glycoprotein (MOG) as a structurally unrelated target. On the other hand, the recombinant N-terminal domain of Nogo-A (residues 334-966) was shown to specifically interact on the Western blot and in an ELISA with the IN-1 F(ab) fragment but not with the recombinant NgR, which is in agreement with previous results. Hence, our data suggest that there is a distinct binding site for the Nogo receptor in the Nogo66 region of Nogo-A, whereas its interaction with NgR is less specific than anticipated before. Although there probably exists a non-linear epitope for the neutralizing antibody IN-1 in the N-terminal region of Nogo-A, which is likely to be accessible from outside the cell, a previously postulated second binding site for NgR in this region (called Nogo-A-24) remains elusive.
Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy (2016)

The B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.).
Non-adherence to the rule of 3 does not increase the risk of adverse events in esophageal dilation (2020)

Although the rule of 3 is recommended to minimize the risk of perforation when esophageal dilation is performed using bougie dilators, there are no data to validate its use. Our aim was to investigate the association between the rule of 3 and adverse events (AEs) in esophageal dilation.
Activated Natural Killer Cell Promotes Nonalcoholic Steatohepatitis Through Mediating JAK/STAT Pathway (2021)

NK cells in NASH liver are activated with a more pro-inflammatory cytokine milieu and promote NASH development via cytokine-JAK-STAT1/3 axis. Modulation of NK cells provides a potential therapeutic strategy for NASH.
Automated reconstruction of the cerebral cortex in multiple sclerosis patients (2009)

Although cortical atrophy in multiple sclerosis (MS) has been reported in the literature, most cortical reconstruction techniques do not account for lesions. In this work, we propose an automated pipeline for cortical reconstruction from magnetic resonance brain images with MS lesions. The pipeline extends previously well validated methods to allow for the presence of lesions and to accommodate multichannel imaging. We validate this approach on simulated and real images. Application of the pipeline to 103 MS brains produces thickness measurements that agree well with the literature.
NMR Measurements of Self-Diffusion in Lithium-Ammonia and Sodium-Ammonia Solutions (1973)

Self-diffusion coefficients of $^{7}\mathrm{Li}$, $^{23}\mathrm{Na}$, and $^{1}\mathrm{H}$ have been measured in 1-20-MPM (100\ifmmode\times\else\texttimes\fi{}moles metal/total of moles metal and moles ammonia) solutions of lithium ammonia at 223 and 233 K and in 2-15.5-MPM solutions of sodium ammonia at 233 K by the NMR spin-echo pulsed-magnetic-field-gradient technique. In addition, the temperature dependences of the self-diffusion coefficients were measured for seven representative concentrations of lithium ammonia below 240 K. The data indicate that the lithium and sodium ions are solvated by four ammonia molecules over the time scale of molecular diffusion. The concentration dependence of the self-diffusion coefficients of the metal-ion complexes and of the free-ammonia molecules is found to be consistent, evaluated by the Stokes-Einstein relation, with the available viscosity data. The melting-point self-diffusion coefficient and the temperature dependence of 20-MPM lithium ammonia are fitted to the Ascarelli-Paskin and Cohen-Turnbull diffusion models for a reasonable choice of packing fraction.
Case Report: Overwhelming Babesia Parasitemia Successfully Treated Promptly With RBC Apheresis and Triple Therapy With Clindamycin, Azithromycin, and Atovaquone (2020)

Babesiosis with high-grade parasitemia is life-threatening, especially in asplenic hosts. We report an asplenic patient with parasitemia >50% who was successfully treated with prompt red blood cell apheresis and triple therapy with clindamycin + azithromycin + atovaquone. This regimen may be an alternative to poorly tolerated clindamycin + quinine in severe cases.
Multi-dimensional computational pipeline for large-scale deep screening of compound effect assessment: an in silico case study on ageing-related compounds (2019)

Designing alternative approaches to efficiently screen chemicals on the efficacy landscape is a challenging yet indispensable task in the current compound profiling methods. Particularly, increasing regulatory restrictions underscore the need to develop advanced computational pipelines for efficacy assessment of chemical compounds as alternative means to reduce and/or replace in vivo experiments. Here, we present an innovative computational pipeline for large-scale assessment of chemical compounds by analysing and clustering chemical compounds on the basis of multiple dimensions-structural similarity, binding profiles and their network effects across pathways and molecular interaction maps-to generate testable hypotheses on the pharmacological landscapes as well as identify potential mechanisms of efficacy on phenomenological processes. Further, we elucidate the application of the pipeline on a screen of anti-ageing-related compounds to cluster the candidates based on their structure, docking profile and network effects on fundamental metabolic/molecular pathways associated with the cell vitality, highlighting emergent insights on compounds activities based on the multi-dimensional deep screen pipeline.
ENDOTHELIAL-CARDIOMYOCYTE INTERACTIONS IN CARDIAC DEVELOPMENT AND REPAIR (2005)

Communication between endothelial cells and cardiomyocytes regulates not only early cardiac development but also adult cardiomyocyte function, including the contractile state. In the normal mammalian myocardium, each cardiomyocyte is surrounded by an intricate network of capillaries and is next to endothelial cells. Cardiomyocytes depend on endothelial cells not only for oxygenated blood supply but also for local protective signals that promote cardiomyocyte organization and survival. While endothelial cells direct cardiomyocytes, cardiomyocytes reciprocally secrete factors that impact endothelial cell function. Understanding how endothelial cells communicate with cardiomyocytes will be critical for cardiac regeneration, in which the ultimate goal is not simply to improve systolic function transiently but to establish new myocardium that is both structurally and functionally normal in the long term.