Miracle-dz/UniFAR-FTUs huggingface dataset:
PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma.

BACKGROUND The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking. PATIENTS AND METHODS We assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients. RESULTS A significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient's outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases. CONCLUSIONS In summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.In spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1.Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.
Sphingomyelin metabolism in erythrocyte membrane in asthma

Background. Sphingomyelin (SM), a major lipid constituent of outer leaflet of plasma membranes, with cholesterol, constitutes microdomains, which are termed as lipid rafts. These rafts provide support to proteins, receptors, enzymes, and so on and organize and orient them to conduct cellular functions including transmembrane signaling to substances in external milieu. The SM contents are regulated by its metabolism, changes in which may affect the composition of lipid rafts and cell response to the triggers of asthma which may lead to the pathophysiology. For studying changes in membranes, erythrocytes, which contain lipid rafts, are considered to be the best cell type. Hence, this study was conducted on plasma membrane of erythrocytes of asthmatic patients. Objective. The objective is to understand the changes in SM metabolism in asthma. Methods. The study included 50 subjects (25 asthmatics and 25 healthy subjects). Erythrocytes were isolated from the peripheral blood and membrane prepared. This was followed by determination of total cholesterol, phospholipids, SM, and sphingomyelinase activity. P < . 05 was considered significant. Results and conclusions In asthmatics, there was a significant decrease in cholesterol contents (p < .05), decrease in total phospholipid contents (p < .005), increase in SM (p < .01), decrease in cholesterol: SM ratio (p < .001) and increase in sphingomyelinase activity (p < .001) in erythrocyte membranes. We conclude that in asthma, the increase in SM contents is associated with increased sphingomyelinase activity which shows an imbalance in SM metabolism, directed toward its accumulation. The ratio of cholesterol to SM, critical for maintenance of lipid rafts, was significantly lower in asthmatics. This indicates changes in structure of lipid rafts which may lead to the pathophysiology and development of asthma. Regulation of SM metabolism may help in disease regulation and its control.
Differences in Production of Reactive Oxygen Species and Mitochondrial Uncoupling as Events in the Preconditioning Signaling Cascade Between Desflurane and Sevoflurane

BACKGROUND: Signal transduction cascade of anesthetic-induced preconditioning has been extensively studied, yet many aspects of it remain unsolved. Here, we investigated the roles of reactive oxygen species (ROS) and mitochondrial uncoupling in cardiomyocyte preconditioning by two modern volatile anesthetics: desflurane and sevoflurane. METHODS: Adult rat ventricular cardiomyocytes were isolated enzymatically. The preconditioning potency of desflurane and sevoflurane was assessed in cell survival experiments by evaluating myocyte protection from the oxidative stress-induced cell death. ROS production and flavoprotein fluorescence, an indicator of flavoprotein oxidation and mitochondrial uncoupling, were monitored in real time by confocal microscopy. The functional aspect of enhanced ROS generation by the anesthetics was assessed in cell survival and confocal experiments using the ROS scavenger Trolox. RESULTS: Preconditioning of cardiomyocytes with desflurane or sevoflurane significantly decreased oxidative stress-induced cell death. That effect coincided with increased ROS production and increased flavoprotein oxidation detected during acute myocyte exposure to the anesthetics. Desflurane induced significantly greater ROS production and flavoprotein oxidation than sevoflurane. ROS scavenging with Trolox abrogated preconditioning potency of anesthetics and attenuated flavoprotein oxidation. CONCLUSION: Preconditioning with desflurane or sevoflurane protects isolated rat cardiomyocytes from oxidative stress-induced cell death. Scavenging of ROS abolishes the preconditioning effect of both anesthetics and attenuates anesthetic-induced mitochondrial uncoupling, suggesting a crucial role for ROS in anesthetic-induced preconditioning and implying that ROS act upstream of mitochondrial uncoupling. Desflurane exhibits greater effect on stimulation of ROS production and mitochondrial uncoupling than sevoflurane.
Investigating Output Accuracy for a Discrete Event Simulation Model and an Agent Based Simulation Model

In this paper, we investigate output accuracy for a Discrete Event Simulation (DES) model and Agent Based Simulation (ABS) model. The purpose of this investigation is to find out which of these simulation techniques is the best one for modelling human reactive behaviour in the retail sector. In order to study the output accuracy in both models, we have carried out a validation experiment in which we compared the results from our simulation models to the performance of a real system. Our experiment was carried out using a large UK department store as a case study. We had to determine an efficient implementation of management policy in the store's fitting room using DES and ABS. Overall, we have found that both simulation models were a good representation of the real system when modelling human reactive behaviour.
Preparation and characterization of ZnO-PP nanocomposite fibers and non-woven fabrics

Abstract In this work, zinc oxide nanorods are synthesized by polyvinyl alcohol-based sol-gel Pyrolysis method and also applied to prepare the antibacterial ZnO/polypropylene nanocomposite fibers and non-woven fabrics. The fibers are produced by the melt spinning and the nonwoven is produced by thermo banding method. The samples are characterized by SEM and TEM. The antibacterial activity of the fibers is qualitative assessed by the agar diffusion and parallel streak and quantitative test methods for percentage reduction of bacteria colonies. The topographical analysis of the treated fiber and untreated fiber are studied and compared. The results show that the treated fibers and non-woven fabrics have the significant antibacterial and antiallergic properties. In addition, the samples show good mechanical strength and UV protection.
P84 Co-Polyimide Based-Tubular Carbon Membrane: Effect of Heating Rates on Helium Separations

Helium is one of the most valuable gases with unique features and properties as well as widely used in various applications. Generally, most of the helium sources was extracted from natural gas and it is very crucial to develop efficient technology for helium recovery from natural gas sources, in order to overcome the deficit of the helium supply. Up to now, there are various available traditional separation methods for helium recovery, however these methods possessed several disadvantages such as expensive in cost and energy intensive. Recently, gas separation by using membranes have been utilized and showed potential in recovering and purifying helium from natural gas. This method directly separating the helium from the methane through natural gas liquefaction process where in this process the helium is recovered from the nitrogen rejection unit (NRU) exit gas. Due to the potential benefits that can be obtained from this membrane-based separation method, this current study is aiming to provide more comprehensive scientific reports on the effects of preparation parameters on the performance of tubular carbon membranes (TCMs) for helium separation. In this study, the carbonization heating rate was varied from 1 to 7°C/min by controlling the final temperature at 800°C under Argon environment for all polymeric tubular membranes. The permeation performance of the resultant TCMs have been determined by using a single permeation apparatus. It is necessary to fine-tuning the carbonization conditions in order to obtain the desired permeation properties. From the results, it can be concluded that the most optimum heating rate was found to be at 3°C/min with 463.86±3.12 selectivity of He/N2 separation.
A Common Suite of Coagulation Proteins Function in Drosophila Muscle Attachment

The organization and stability of higher order structures that form in the extracellular matrix (ECM) to mediate the attachment of muscles are poorly understood. We have made the surprising discovery that a subset of clotting factor proteins are also essential for muscle attachment in the model organism Drosophila melanogaster. One such coagulation protein, Fondue (Fon), was identified as a novel muscle mutant in a pupal lethal genetic screen. Fon accumulates at muscle attachment sites and removal of this protein results in decreased locomotor behavior and detached larval muscles. A sensitized genetic background assay reveals that fon functions with the known muscle attachment genes Thrombospondin (Tsp) and Tiggrin (Tig). Interestingly, Tig is also a component of the hemolymph clot. We further demonstrate that an additional clotting protein, Larval serum protein 1γ (Lsp1γ), is also required for muscle attachment stability and accumulates where muscles attach to tendons. While the local biomechanical and organizational properties of the ECM vary greatly depending on the tissue microenvironment, we propose that shared extracellular protein–protein interactions influence the strength and elasticity of ECM proteins in both coagulation and muscle attachment.
Using WordNet for Opinion Mining

This paper deals with lexical resources applied for opinion mining ‐ the identification and extraction of opinions from free texts. Opinion mining comprises the segmentation of documents, passages, sentences, or phrases to objective (factual) and subjective parts, and the evaluation of the subjective attitude toward a given fact. We briefly introduce an automatic system that was designed to crawl various information sources available on the Web ‐ newspapers, Internet blogs and forums ‐ to collect and identify different opinions on a given topic and to report diversity of opinions across languages and countries. A special attention is paid to linguistic resources used, especially to wordnet extensions that play a crucial role in the identification of subjective expressions.
Subcutaneous immunization with recombinant adenovirus expressing influenza A nucleoprotein protects mice against lethal viral challenge

Current influenza vaccines mainly induce strain-specific neutralizing antibodies and need to be updated each year, resulting in significant burdens on vaccine manufacturers and regulatory agencies. Genetic immunization strategies based on the highly conserved nucleoprotein (NP) of influenza have attracted great attention as NP could induce heterosubtypic immunity. It is unclear, however, whether different forms of vectors and/or vaccination regimens could have contributed to the previously reported discrepancies in the magnitude of protection of NP-based genetic vaccinations. Here, we evaluated a plasmid DNA vector (pNP) and a recombinant adenovirus vector (rAd-NP) containing the NP gene through various combinations of immunization regimens in mice. We found that pNP afforded only partial protection even after 4 injections, with full protection against lethal challenge achieved only with the fourth boost using rAd-NP. Alternatively, only two doses of rAd-NP delivered subcutaneously were needed to induce an enhanced immune response and completely protect the animals, a finding which, to our knowledge, has not been reported before.
Penicillium kongii, a new terverticillate species isolated from plant leaves in China

A new Penicillium species isolated from plant leaves, characterized by restricted growth, terverticillate penicilli, ovoid to ellipsoidal conidia and a red soluble pigment on yeast extract sucrose agar is reported here. Penicillium kongii sp. nov. belongs to subgenus Penicillium section Brevicompacta and is morphologically similar to P. bialowiezense and P. brevicompactum. Phylogenetic analyses based on sequence data from calmodulin gene, β-tubulin gene and rDNA ITS1-5.8S-ITS2 show that P. kongii forms a distinctive clade.
Enhancing the mechanical properties of low-carbon steel by a graded dislocation microstructure

ABSTRACT In the present paper, the microstructures and mechanical properties of a low-carbon steel processed by graded pre-torsion (PTO) and homogeneous pre-tension (PTE), respectively, have been investigated. Experimental results demonstrate that both PTO and PTE can improve the strength of the low-carbon steel, but at a loss of ductility and toughness. However, a much better strength–ductility–toughness synergy is achieved in samples processed by graded PTO than that in samples subjected to PTE. This enhancement of comprehensive mechanical properties is due to the formation of a graded microstructure, that is, the dislocation-density increases gradually with decreasing the depth from the sample surface. This study provides a strategy for enhancing the mechanical properties of metallic materials by graded plastic deformation.
Termination of Epileptic Afterdischarge in the Hippocampus Materials and Methods

The mechanism of afterdischarge termination in the various hippocampal regions was examined in the rat. Stimulation of the perforant path or the commissural system was used to elicit afterdischarges. Combination of multiple site recordings with silicon probes, current source density analysis, and unit recordings in the awake animal allowed for a high spatial resolution of the field events. Interpretation of the field observations was aided by intracellular recordings from anesthetized rats. Irrespective of the evoking conditions, afterdischarges always terminated first in the CA1 region. Termination of the afterdis-charge was heralded by a large DC shift initiated in dendritic layers associated with a low amplitude " afterdischarge termination oscillation " (ATO) at 40 to 80 Hz in the cell body layer. ATOs were also observed in the CA3 region and the dentate gyrus. The DC shift spread at the same velocity (0.1– 0.2 mm/ sec) in all directions and could cross the hippocampal fissure. All but 1 of the 25 putative interneurons in the CA1 and dentate regions ceased to fire before the onset of ATO. Intracellularly, ATO and the emerging DC potential were associated with fast depolarizing potentials and firing of pyramidal cells and depo-larization block of spike initiation, respectively. Both field ATO and the intracellular depolarization shift were replicated by focal microinjection of potassium. We hypothesize that [K ϩ ] o lost by the intensely discharging neurons during the afterdis-charge triggers propagating waves of depolarization in the astrocytic network. In turn, astrocytes release potassium, which induces a depolarization block of spike generation in neurons, resulting in " postictal depression " of the EEG. The most common form of seizures, complex partial epilepsy, arises in the hippocampal region (cf. Engel, 1989; McNamara, 1994). The seizures are often followed by depressed electrical activity, termed " postictal silence " (Engel, 1989). Numerous in vivo and in vitro models of epilepsy have investigated the emergence , maintenance, and spread of seizures. In contrast, relatively few studies have specifically addressed the issue of seizure termi-The issue is important because understanding factors critically involved in ending an ongoing seizure may lead to a more effective treatment of epileptic patients. The goal of the present investigation was to reveal the contribution of the various factors responsible for the termination of stimulation-induced afterdischarges in the intact brain. The lam-inar neuronal organization of the hippocampus (Amaral and Witter, 1989) makes this structure particularly relevant to investigate population synchrony …
Refreshment policies for Web content caches

Web content caches are often placed between end-users and origin servers as a mean to reduce server load, network usage, and ultimately, user-perceived latency. Cached objects typically have associated expiration times, after which they are considered stale and must be validated with a remote server (origin or another cache) before they can be sent to a client. A considerable fraction of cache hits involve stale copies that turned out to be current. These validations of current objects have small message size, but nonetheless, often induce latency comparable to full-fledged cache misses. Thus, the functionality of caches as a latency-reducing mechanism highly depends not only on content availability but also on its freshness. We propose policies for caches to preactively validate selected objects as they become stale, and thus allow for more client requests to be processed locally. Our policies operate within the existing protocols and exploit natural properties of request patterns such as frequency and recency. We evaluated and compared different policies using trace-based simulations.
Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice

Pleckstrin homology-like domain family A member 2 (PHLDA2) is a maternally expressed imprinted gene whose elevated expression has been linked to fetal growth restriction in a number of human studies. In mice, Phlda2 negatively regulates placental growth and limits the accumulation of placental glycogen. We previously reported that a three-copy transgene spanning the Phlda2 locus drove a fetal growth restriction phenotype late in gestation, suggesting a causative role for PHLDA2 in human growth restriction. However, in this mouse model, Phlda2 was overexpressed by fourfold, alongside overexpression of a second imprinted gene, Slc22a18. Here, we genetically isolate the role of Phlda2 in driving late fetal growth restriction in mice. We furthermore show that this Phlda2-driven growth restriction is asymmetrical, with a relative sparing of the brain, followed by rapid catch-up growth after birth, classic features of placental insufficiency. Strikingly, fetal growth restriction showed strain-specific differences, being apparent on the 129S2/SvHsd (129) genetic background and absent on the C57BL6 (BL6) background. A key difference between these two strains is the placenta. Specifically, BL6 placentae possess a more extensive endocrine compartment and substantially greater stores of placental glycogen. Taken together, these data support a direct role for elevated Phlda2 in limiting fetal growth but also suggest that growth restriction only manifests when there is limited placental reserve. These findings should be taken into account in interpreting the results from human studies.
Recent advances: control of chronic pain.

The most important clinical development in chronic pain during the past decade has not been new treatments but a thoroughly revised interpretation of the mechanisms that act to maintain pain. Pain is no more seen as a predetermined result of simple activation of certain neural structures. It is now understood to be a dynamic phenomenon due to myriad pathophysiological changes in the peripheral and central nervous system in response to disease, injury, or loss of function1 (box 1). These changes reflect the surprising but indisputable fact that the human nervous system is adaptable and capable of substantial plasticity. Initially reversible, the changes tend to become fixed depending on the nature and duration of the original cause, as well as the age and perhaps the genetic susceptibility of the patient In chronic pain the abnormal activity in the altered pain mediating afferent system continues irrespective of its original causation. Simple blocking or severing of neural pathways is not helpful: the locus of abnormal barrages is simply shifted more centrally. Recent advances in the pharmacology of pain have unravelled some of the mediators of chronic pain, and they offer potential targets for treatments that are currently being developed (box 2). New investigative techniques are also being developed for improved detection of factors maintaining chronic pain. Alongside pharmacological advances, stimulation treatments and psychological approaches have seen innovative developments. ### Recent advances Chronic pain is now known to be maintained by several pathophysiological mechanisms which currently can be dealt with only partially New generation non-steroidal anti-inflammatory drugs have been developed for the treatment of rheumatic pain, but their true potential awaits the test of time Choices for the treatment of neuropathic pain have increased with the advent of new anticonvulsants and topical agents Indications for spinal cord stimulation have widened and include chronic angina and peripheral …
Learning curve for breast mass excision using a vacuum-assisted biopsy system

Abstract Background : Vacuum-assisted breast biopsy system (VAB) is an alternative modality to core needle biopsy for the diagnosis of breast lesions. Material and methods : Fifty-four patients who underwent ultrasound-guided VAB procedures were analyzed. Patients were categorized into two groups: The first 20 consecutive patients as group A and the next 34 consecutive patients as group B. Results : Fifty-two patients underwent excision, and two underwent biopsy only. Moving average curves showed a plateau phase for performing VAB procedures after the 20th patient. Total operation times of group B were significantly shorter than those of group A (p < 0.001). Complication rates in group B tended to be lower, and VAB probe position of group B tended to be better than that of group A, but these differences were not statistically significant. Conclusion : Our data suggest the existence of a learning curve for ultrasound-guided VAB procedures. VAB procedures can be performed safely, even during the early learning period.