gebhart/patrepeval huggingface dataset:
Combination therapy strategies for improving PD‐1 blockade efficacy: a new era in cancer immunotherapy (2017)

Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively regulates T-cell immune function through the interaction with its ligand PD-L1. Blockage of this interaction unleashes the immune system to fight cancer. Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of cancer drug discovery, owing to its durable effect against a wide variety of cancers with limited adverse effects. A brief history and development of PD-1 blockade, from the initial discovery of PD-1 to the recent clinical output of this therapy, have been summarized here. Despite its tremendous clinical success rate over other cancer treatments, PD-1 blockade has its own pitfall; a significant fraction of patients remains unresponsive to this therapy. The key to improve the PD-1 blockade therapy is the development of combination therapies. As this approach has garnered worldwide interest, here, we have summarized the recent trends in the development of PD-1 blockade-based combination therapies and the ongoing clinical trials. These include combinations with checkpoint inhibitors, radiation therapy, chemotherapy and several other existing cancer treatments. Importantly, FDA has approved PD-1 blockade agent to be used in combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD-1 blockade therapy is affected by tumour and immune system-related factors. The role of the immune system, especially T cells, in determining the responsiveness has been poorly studied compared with those factors related to the tumour side. Energy metabolism has emerged as one of the important regulatory mechanisms for the function and differentiation of T cells. We have documented here the recent results regarding the augmentation of PD-1 blockade efficacy by augmenting mitochondrial energy metabolism of T cell.
The Long-Term Effect of a Nine Amino-Acid Antimicrobial Peptide AS-hepc3(48-56) Against Pseudomonas aeruginosa With No Detectable Resistance (2021)

The emergence of multidrug-resistant (MDR) pathogens has become a global public health crisis. Among them, MDR <i>Pseudomonas aeruginosa</i> is the main cause of nosocomial infections and deaths. Antimicrobial peptides (AMPs) are considered as competitive drug candidates to address this threat. In the study, we characterized two AMPs (AS-hepc3<sub>(41-71)</sub> and AS-hepc3<sub>(48-56)</sub>) that had potent activity against 5 new clinical isolates of MDR <i>P. aeruginosa</i>. Both AMPs destroyed the integrity of the cell membrane, induced leakage of intracellular components, and ultimately led to cell death. A long-term comparative study on the bacterial resistance treated with AS-hepc3<sub>(41-71)</sub>, AS-hepc3<sub>(48-56)</sub> and 12 commonly used antibiotics showed that <i>P. aeruginosa</i> quickly developed resistance to the nine antibiotics tested (including aztreonam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, gentamicin, and piperacillin) as early as 12 days after 150 days of successive culture generations. The initial effective concentration of 9 antibiotics against <i>P. aeruginosa</i> was greatly increased to a different high level at 150 days, however, both AS-hepc3<sub>(41-71)</sub> and AS-hepc3<sub>(48-56)</sub> maintained their initial MIC unchangeable through 150 days, indicating that <i>P. aeruginosa</i> did not produce any significant resistance to both AMPs. Furthermore, AS-hepc3<sub>(48-56)</sub> did not show any toxic effect on mammalian cells <i>in vitro</i> and mice <i>in vivo</i>. AS-hepc3<sub>(48-56)</sub> had a therapeutic effect on MDR <i>P. aeruginosa</i> infection using a mouse lung infection model and could effectively increase the survival rate of mice by inhibiting bacterial proliferation and attenuating lung inflammation. Taken together, the short peptide AS-hepc3<sub>(48-56)</sub> would be a promising agent for clinical treatment of MDR <i>P. aeruginosa</i> infections.
Toluidine Blue Staining Identifies High-Risk Primary Oral Premalignant Lesions with Poor Outcome (2005)

There is a pressing need for the development of visual aids that will facilitate the detection of oral premalignant lesions (OPLs) with a high-risk of progression. Preliminary data suggest that toluidine blue stain may be preferentially retained by OPLs with high-risk molecular clones. In this study, we monitored OPLs from 100 patients without any history of oral cancer for an average of 44 months in order to evaluate the association of toluidine blue status with clinicopathologic risk factors, molecular patterns (microsatellite analysis on seven chromosome arms: 3p, 9p, 4q, 8p, 11q, 13q, and 17p) and outcome. Toluidine blue-positive staining correlated with clinicopathologic risk factors and high-risk molecular risk patterns. Significantly, a >6-fold elevation in cancer risk was observed for toluidine blue-positive lesions, with positive retention of the dye present in 12 of the 15 lesions that later progressed to cancer (P = 0.0008). This association of toluidine blue status with risk factors and outcome was evident even when the analysis was restricted to OPLs with low-grade or no dysplasia. Our results suggest the potential use of toluidine blue in identifying high-risk OPLs.
Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators (2013)

Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening complication of the administration of PN. The development of PNALD may be partly due to the composition of the lipid emulsion administered with PN: soybean oil-based lipid emulsions (SOLE) are associated with liver disease, while fish oil-based lipid emulsions (FOLE) are associated with prevention and improvement of liver disease. The objective of this study was to determine how the choice of lipid emulsion modified the production of bioactive lipid mediators (LMs). We utilized a mouse model of steatosis to study the differential effect of FOLE and SOLE. We subsequently validated these results in serum samples from a small cohort of human infants transitioning from SOLE to FOLE. In mice, FOLE was associated with production of anti-inflammatory, proresolving LMs; SOLE was associated with increased production of inflammatory LMs. In human infants, the transition from SOLE to FOLE was associated with a shift toward a proresolving lipidome. Together, these results demonstrate that the composition of the lipid emulsion directly modifies inflammatory homeostasis.
Network virtualization tools – analysis and application in higher education (2019)

The education of networking professionals requires not only the knowledge of theory but also acquiring practical skills. For this purpose, specialized networking laboratories equipped with the required diverse technology have been built for years. However, building them is lengthy, expensive, and ultimately laboratories have several limitations, for example in terms of flexibility, sustainability, financial and energy demands, etc. In recent years has begun to intensively evolve the trend of virtualization, both networks as well as computers, that is allowing the development and deployment of more flexible types of virtualized lab solutions. Usually, a general computer hardware and virtualization software are used to operate them. We consider, that this trend of virtualization becomes important and decisive for the coming period. The article focuses therefore on a wider analysis and description of available virtualization solutions specifically aimed at the teaching of network-related university subjects and networking education. At the same time, the article offers a look at our way of using these tools in our everyday teaching process and what experience we have gained from their implementation and usage.
Attention Deficits and Hyperactivity in Children (1994)

This is a concise, state-of-the-art synthesis of the vast amount of information related to attention deficits and hyperactivity in children. The author explores key issues such as: whether there is in fact a valid syndrome; which factors predict subsequent adolescent and adult functioning; and the most suitable assessment instruments. The volume encompasses a wide range of perspectives, including clinical, developmental, psychodiagnostic, psychobiological, environmental//familial and social cognitive.
Antibacterial Activity of a Novel Peptide-Modified Lysin Against Acinetobacter baumannii and Pseudomonas aeruginosa (2015)

The global emergence of multidrug-resistant (MDR) bacteria is a growing threat to public health worldwide. Natural bacteriophage lysins are promising alternatives in the treatment of infections caused by Gram-positive pathogens, but not Gram-negative ones, like Acinetobacter baumannii and Pseudomonas aeruginosa, due to the barriers posed by their outer membranes. Recently, modifying a natural lysin with an antimicrobial peptide was found able to break the barriers, and to kill Gram-negative pathogens. Herein, a new peptide-modified lysin (PlyA) was constructed by fusing the cecropin A peptide residues 1-8 (KWKLFKKI) with the OBPgp279 lysin and its antibacterial activity was studied. PlyA showed good and broad antibacterial activities against logarithmic phase A. baumannii and P. aeruginosa, but much reduced activities against the cells in stationary phase. Addition of outer membrane permeabilizers (EDTA and citric acid) could enhance the antibacterial activity of PlyA against stationary phase cells. Finally, no antibacterial activity of PlyA could be observed in some bio-matrices, such as culture media, milk, and sera. In conclusion, we reported here a novel peptide-modified lysin with significant antibacterial activity against both logarithmic (without OMPs) and stationary phase (with OMPs) A. baumannii and P. aeruginosa cells in buffer, but further optimization is needed to achieve broad activity in diverse bio-matrices.
Topological shape optimization design of continuum structures via an effective level set method (2016)

Abstract This paper proposes a new level set method for topological shape optimization of continuum structure using radial basis function (RBF) and discrete wavelet transform (DWT). The boundary of the structure is implicitly represented as the zero level set of a higher-dimensional level set function. The interpolation of the implicit surface using RBF is introduced to decouple the spatial and temporal dependence of the level set function. In doing so, the Hamilton-Jacobi partial differential equation (PDE) that defines the motion of the level set function is transformed into an explicit parametric form, without requiring the direct solution of the complicated PDE using the finite difference method. Therefore, many more efficient gradient-based optimization algorithms can be applied to solve the optimization problem, via updating the expansion coefficients of the interpolant and then evolving the level set function and the boundary. Furthermore, the DWT is employed to handle the full matrix arising from the globally supported RBF interpolation. Several high stiffness but lightweight designs with smooth and clear structural boundaries are optimized and presented. The numerical results show that the proposed method can remarkably increase the efficiency in the topology optimization design of both the 2D and 3D structures.
Quantitative thermal measurement by the use of scanning thermal microscope and resistive thermal probes (2020)

Scanning thermal microscopy (SThM) is the only method for thermal measurements providing spatial resolution in the nanometer range. The method combines the topographical imaging of atomic force microscopy (AFM) with the thermal characterization of samples by the use of specially designed AFM probes having a temperature sensor near the apex. Measurements can be carried out in two modes: the temperature contrast (or passive) mode and the conductance contrast (or active) mode. In the first mode, the probe is not heated and the temperature distribution on the sample surface is measured. In the second mode, there are no heat sources in the sample and the probe is heated. The probe temperature depends on the thermal conductance for the heat exchange between the probe and the sample. This thermal conductance depends on the sample thermal conductivity and probe-sample interfacial thermal resistance. If the latter is constant, the distribution of the thermal conductivity on the sample surface can be obtained. The principle of qualitative SThM is quite simple. However, quantitative measurements require rigorous analysis of temperature distribution and heat fluxes in the probe-sample system. This paper provides basic information about SThM starting from first principles, through instrumentation, characterization of probes used for measurements, general theory of the temperature, and the thermal conductivity measurements, to a few examples of practical applications of this method. Finally, perspectives and challenges for SThM based measurements are discussed.
Vanadium dioxide reconfigurable slot antenna (2016)

A novel method for reconfigurable antennas that utilize the unique properties of phase-change materials has recently been demonstrated using a metallic bowtie dipole antenna. Here, a reconfigurable coplanar folded slot antenna prototype with Vanadium Dioxide (VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) is presented. The antenna has the ability to alter its resonant frequency with temperature. The main design methodology and design characteristics are presented. This technology can lead to advanced designs and devices that employ phase-change materials as their reconfiguration method. Additional results from different antennas, integration challenges, and potential capabilities will be presented.
<i>mild®</i> Lumbar Decompression for the Treatment of Lumbar Spinal Stenosis (2011)

More than 1.2 million people are undergoing treatment for lumbar spinal stenosis (LSS) in the United States. Yet, therapeutic options for these patients are limited to either conservative treatments or highly invasive surgeries. A new image-guided interlaminar decompression procedure, mild(®), offers significant relief for many of these patients by debulking dorsal element hypertrophy while preserving structural stability. mild can be performed without general anesthesia and offers a short recovery period. A meta-analysis of four clinical patient series from multiple institutions in the United States evaluated over 250 patients for safety and clinical efficacy of the mild procedure. Clinical efficacy was evaluated at baseline and at three-month follow-up using validated patient reported outcomes (PRO) instruments including the ten-point Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). Acute safety and patient outcomes was compared to the Spine Patient Outcomes Research Trial (SPORT). No device or procedure-related serious adverse events (SAEs) have been recorded with the mild procedure. Outcome metrics for patients treated with mild demonstrated statistically significant symptomatic improvement over baseline. When compared to open surgery, mild efficacy results compare favorably, and complication rates are much lower. mild is a safe and effective procedure that decompresses LSS in a minimally invasive manner while preserving the structural stability of the spine.
Ebola virus persistence and disease recrudescence in the brains of antibody-treated nonhuman primate survivors (2022)

Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence and associated disease recrudescence in survivors receiving these therapeutics remains unclear. In contrast to rhesus macaques that survived Ebola virus (EBOV) exposure in the absence of treatment, we discovered that EBOV, despite being cleared from all other organs, persisted in the brain ventricular system of rhesus macaque survivors that had received monoclonal antibody (mAb) treatment. In mAb-treated macaque survivors, EBOV persisted in macrophages infiltrating the brain ventricular system, including the choroid plexuses. This macrophage infiltration was accompanied by severe tissue damage, including ventriculitis, choroid plexitis, and meningoencephalitis. Specifically, choroid plexus endothelium-derived EBOV infection led to viral persistence in the macaque brain ventricular system. This resulted in apoptosis of ependymal cells, which constitute the blood-cerebrospinal fluid barrier of the choroid plexuses. Fatal brain-confined recrudescence of EBOV infection manifested as severe inflammation, local pathology, and widespread infection of the ventricular system and adjacent neuropil in some of the mAb-treated macaque survivors. This study highlights organ-specific EBOV persistence and fatal recrudescent disease in rhesus macaque survivors after therapeutic treatment and has implications for the long-term follow-up of human survivors of EVD.
Comparison of surface and bulk scattering in optical multilayers (1993)

Electromagnetic theories provide a tool to detect the origin of scattering in optical multilayers. Illumination and observation conditions that cause surface and bulk scatterings to have different behaviors are pointed out. Angular, wavelength, and polarization dependences are investigated for the location of structural irregularities at interfaces or in the bulk of a multilayer. Specific experiments can be designed.
Correction of metabolic acidosis after conversion from sevelamer hydrochloride to lanthanum carbonate (2008)

Correction of metabolic acidosis after conversion from sevelamer hydrochloride to lanthanum carbonate
Scutellarin Attenuates Oxidative Glutamate Toxicity in PC12 Cells (2004)

The present study investigated the protective effects of the antioxidant scutellarin against oxidative toxicity induced by glutamate in PC12 cells. Vitamin E, a classical antioxidant was employed as a comparative agent. Incubation of PC12 cells with 10 mM glutamate resulted in significant cytotoxity as evaluated by the MTT and lactate dehydrogenase (LDH) assays, decreases of GSSG reductase activity, disturbance of the cell redox state as indicated by the GSH/GSSG ratio, and accumulation of intracellular reactive oxygen species (ROS) and lipid peroxidation products. Scutellarin at 0.1, 1 and 10 microM significantly protected against the cytoxicity and production of ROS and lipid peroxidation induced by glutamate. Scutellarin did not prevent the reduction of cellular GSH levels, but it up-regulated GSSG reductase activity, thus preventing an increase in cellular GSSG levels, and concomitantly improved the cell redox status. Our data also show that the protective effects of scutellarin against glutamate-induced oxidative toxicity are more potent than that of vitamin E. These results demonstrate that scutellarin can protect PC12 cells from oxidative glutamate toxicity by scavenging ROS, inhibiting lipid peroxidation and improving the cell redox status, and may reduce the cellular damage in pathological conditions associated with excessive glutamate release.
Influence of Environmental Temperature on the Blood Pressure of Hypertensive Patients in Montreal (1991)

To assess the influence of environmental temperature on blood pressure, we analyzed 42,813 readings of systolic and diastolic blood pressures in recumbent and upright positions in 2,000 hypertensive patients in our clinic in correlation to noon temperature and mean daily temperature in Montréal. The sample comprised 860 men and 1140 women with an average age of 55 years. Analysis of variance showed highly statistically significant negative correlations for all blood pressure values between different noon temperature, as well as mean daily temperature, groups. The greatest difference for systolic blood pressure was 7 mm Hg, and for diastolic blood pressure it was 3 mm Hg, within the -24 degrees C to 27 degrees C temperature range. The same relationship between blood pressure and different environmental temperatures was also seen when the blood pressure recordings were divided between temperature below 0 degree C and above 0 degree C, ie, within the winter or summer months. This environmental effect may have a clinically significant impact because thermosensitivity appears to be related to hypertension.
Permanent acceptance of liver allografts by intraportal injection of donor spleen cells in rats. (1992)

Antigen pretreatment through the oral or intraportal route has been reported to suppress antibody formation or delayed-type hypersensitivity (DTH) response to the same antigens. However, this effect on allografted organs has not been well studied. In this study we evaluated the efficacy for suppression of antibody formation and DTH response to the allogeneic antigens and tried to prolong liver allograft survival in rats. Male ACI (RT1a) rats were used as donors and male BUF (RT1b) rats as recipients. Intraportal or intravenous injection of spleen cells (SPCs) (5 x 10(7)) was performed through the mesenteric vein or the tail vein, respectively. The anti-ACI DTH response was tested by ear challenge of ACI SPCs. Cytotoxic antibody was assessed by complement-dependent cytotoxicity assay. ACI rat liver was transplanted orthotopically to BUF rat by the cuff technique 10 days after SPC injection. Cytotoxic antibody titer rose to X2(6) to X2(8) at 7 to 10 days after intravenous injection of SPCs. However, intraportal injection of the cells rarely caused a rise in antibody titer and even strongly suppressed subsequent antibody formation induced by intravenous injection when given 10 days before. The DTH response was also suppressed by intraportal injection of SPCs, with a mean value of 0.18 +/- 0.13 mm versus 0.67 +/- 0.19 mm for controls or 0.46 +/- 0.04 mm with intravenous injection. Liver-allografted rats died between 9 and 11 days, averaging 10.1 +/- 0.7 days in the control group. All seven transplants injected intraportally with donor SPCs survived more than 100 days, whereas six of eight rats injected intravenously with donor SPCs died of bleeding from the surface of the liver grafts within 12 hours after grafting, with signs similar to those of hyperacute rejection. Four of five rats injected intraportally with F344 (third-party) SPCs died of acute rejection in the same way the control rats died. The liver allograft-bearing rats had permanently accepted ACI skin grafts when tested 60 days after liver transplantation but rejected F344 skin grafts in the normal fashion. Intraportal injection of donor SPCs markedly suppressed the antibody formation, as well as the DTH response, and completely blocked liver allograft rejection. Moreover, the liver allograft-bearing rats proved to be fully tolerant of the donor antigen. This method might be a promising modality for inducing donor-specific tolerance in liver transplantation.