gebhart/patrepeval huggingface dataset:
Is exhaled carbon monoxide level associated with blood glucose level? A comparison of two breath analyzing methods (2008)

The level of exhaled carbon monoxide (eCO) is considered a marker of oxidative stress in diabetes. Previous findings indicated that eCO levels correlated with blood glucose level. The aim of this work was to apply and compare two independent analyzing methods for eCO after oral glucose administration. Glycemia, eCO, and exhaled hydrogen were measured before and after oral administration of glucose. Six healthy nonsmoking volunteers participated. For eCO analysis, we used two methods: a commercially available electrochemical sensor, and a high-precision laser spectrometer developed in our laboratory. The precision of laser-spectroscopic eCO measurements was two orders of magnitude better than the precision of the electrochemical eCO measurement. eCO levels measured by laser spectrometry after glucose administration showed a decrease of 4.1%+/-1.5% compared to the baseline (p<0.05). Changes in the eCO measured by the electrochemical sensor were not significant (p=0.08). Exhaled hydrogen levels increased by 40% within the first 10 min after glucose administration (p<0.05). The previous finding that the glycemia increase after glucose administration was associated with a significant increase in eCO concentrations was not confirmed. We propose that previous eCO measurements with electrochemical sensors may have been affected by cross sensitivity to hydrogen.
Cystatin E is a Novel Human Cysteine Proteinase Inhibitor with Structural Resemblance to Family 2 Cystatins (1997)

A new member of the human cystatin superfamily, called cystatin E, has been found by expressed sequence tag (EST) sequencing in amniotic cell and fetal skin epithelial cell cDNA libraries. The sequence of a full-length amniotic cell cDNA clone contained an open reading frame encoding a putative 28-residue signal peptide and a mature protein of 121 amino acids, including four cysteine residues and motifs of importance for the inhibitory activity of Family 2 cystatins like cystatin C. Recombinant cystatin E was produced in a baculovirus expression system and isolated. An antiserum against the recombinant protein could be used for affinity purification of cystatin E from human urine, as confirmed by N-terminal sequencing. The mature recombinant protein processed by insect cells started at amino acid 4 (cystatin C numbering), and displayed reversible inhibition of papain and cathepsin B (Ki values of 0.39 and 32 nM, respectively), in competition with substrate. Cystatin E is thus a functional cysteine proteinase inhibitor despite relatively low amino acid sequence similarities with human cystatins (26-34% identity with sequences for the Family 2 cystatins C, D, S, SN, and SA; <30% with the Family 1 cystatins, A and B, and domains 2 and 3 of the Family 3 cystatin, kininogen). Unlike other human low Mr cystatins, cystatin E is a glycoprotein, carrying an N-linked carbohydrate chain at position 108. Northern blot analysis revealed that the cystatin E gene is expressed in most human tissues, with the highest mRNA amounts found in uterus and liver. A strikingly high incidence of cystatin E clones in cDNA libraries from fetal skin epithelium and amniotic membrane cells (>0.5% of clones sequenced) indicates a protective role of cystatin E during fetal development.
Small RNA Regulators of T Cell-Mediated Autoimmunity (2010)

In this review,we highlight generalmodes of miRNA function and relate them to how such regulation can be beneficial for immune homeostasis and the prevention of autoimmune diseases.We highlight examples of experimentally verified miRNA function and their target genes in the immune system and place them in context of concepts relevant to an understanding of autoimmune pathogenesis. Where available, we refer to clinical correlations. Finally, we speculate how emerging knowledge about miRNA function in the immune system might be used diagnostically and therapeutically.
BSACI guidelines for the management of rhinosinusitis and nasal polyposis (2007)

This guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.
Clinicopathological Aspects of Small Pancreatic Cancer (2004)

Small pancreatic cancers, intractable diseases, offer the possibility of cure. Can this be true? Through the National Pancreatic Cancer Registry, the Japan Pancreas Society (JPS) has collected 822 cases of invasive cancer with tumors <2 cm in diameter (TS1 pancreatic cancer). Papillary adenocarcinoma and the well-differentiated type of tubular adenocarcinoma are more frequent in TS1 pancreatic cancer than the larger tumors, suggesting that further genetic and phenotypic changes occur during their progression. Patients with TS1 pancreatic cancer presented with abdominal pain, jaundice, and exacerbation of diabetes, while 17.3% of them had no symptoms. Further imaging diagnosis should be employed to detect TS1 pancreatic cancer, but conventional US and ERCP play an important role in the diagnostic process. In this study, of 822 patients with TS1 pancreatic cancer, only 216 patients (26.3%) had T1 tumors because of invasion to adjacent tissue. There were 306 patients (37.2%) with lymph node metastasis, of whom 63 (7.7%) had N3 metastasis that is counted as a distant metastasis. As a result, only 136 patients (16.5%) had stage I disease with a median survival time of 78.2 months and a 5-year survival rate of 58.1%. Small pancreatic cancer does not necessarily mean early pancreatic cancer, and surgery alone is not sufficient to cure this disease.
Efficient Eradication of Mature Pseudomonas aeruginosa Biofilm via Controlled Delivery of Nitric Oxide Combined with Antimicrobial Peptide and Antibiotics (2016)

Fast eradication of mature biofilms is the 'holy grail' in the clinical management of device-related infections. Endogenous nitric oxide (NO) produced by macrophages plays an important role in host defense against intracellular pathogens, and NO is a promising agent in preventing biofilms formation in vitro. However, the rate of delivery of NO by various NO donors (e.g., diazeniumdiolates, S-nitrosothiols, etc.) is difficult to control, which hinders fundamental studies aimed at understanding the role of NO in biofilm control. In this study, by using a novel precisely controlled electrochemical NO releasing catheter device, we examine the effect of physiological levels of NO on eradicating mature Pseudomonas aeruginosa biofilm (7 days), as well as the potential application of the combination of NO with antimicrobial agents. It is shown that physiological levels of NO exhibit mixed effects of killing bacteria and dispersing ambient biofilm. The overall biofilm-eradicating effect of NO is quite efficient in a dose-dependent manner over a 3 h period of NO treatment. Moreover, NO also greatly enhances the efficacy of antimicrobial agents, including human beta-defensin 2 (BD-2) and several antibiotics, in eradicating biofilm and its detached cells, which otherwise exhibited high recalcitrance to these antimicrobial agents. The electrochemical NO release technology offers a powerful tool in evaluating the role of NO in biofilm control as well as a promising approach when combined with antimicrobial agents to treat biofilm-associated infections in hospital settings, especially infections resulting from intravascular catheters.
Extracellular High Mobility Group Box-1 (HMGB1) Inhibits Enterocyte Migration via Activation of Toll-like Receptor-4 and Increased Cell-Matrix Adhesiveness (2009)

Toll-like receptor-4 (TLR4) is the receptor for bacterial lipopolysaccharide, yet it may also respond to a variety of endogenous molecules. Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in newborn infants and is characterized by intestinal mucosal destruction and impaired enterocyte migration due to increased TLR4 signaling on enterocytes. The endogenous ligands for TLR4 that lead to impaired enterocyte migration remain unknown. High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. We thus hypothesize that extracellular HMGB1 inhibits enterocyte migration via activation of TLR4 and sought to define the pathways involved. We now demonstrate that murine and human NEC are associated with increased intestinal HMGB1 expression, that serum HMGB1 is increased in murine NEC, and that HMGB1 inhibits enterocyte migration in vitro and in vivo in a TLR4-dependent manner. This finding was unique to enterocytes as HMGB1 enhanced migration of inflammatory cells in vitro and in vivo. In seeking to understand the mechanisms involved, TLR4-dependent HMGB1 signaling increased RhoA activation in enterocytes, increased phosphorylation of focal adhesion kinase, and increased phosphorylation of cofilin, resulting in increased stress fibers and focal adhesions. Using single cell force traction microscopy, the net effect of HMGB1 signaling was a TLR4-dependent increase in cell force adhesion, accounting for the impaired enterocyte migration. These findings demonstrate a novel pathway by which TLR4 activation by HMGB1 delays mucosal repair and suggest a novel potential therapeutic target in the amelioration of intestinal inflammatory diseases like NEC.
Activation of the Wnt Pathway Interferes with Serum Response Element-driven Transcription of Immediate Early Genes (2002)

Mutational activation of the Wnt signaling pathway is a common early event in colorectal tumorigenesis, and the identification of target genes regulated by this pathway will provide a better understanding of tumor progression. Gene expression profiling on oligonucleotide microarrays revealed reduced expression of the immediate early genes fos and fosB following stimulation of cells by Wnt-1. Further analysis demonstrated that serum or 12-O-tetradecanoylphorbol-13-acetate activation of several immediate early genes including fos, fosB, junB, and egr1 was inhibited by Wnt signaling. Wnt signaling inhibited transcriptional activation driven by the serum response element without altering the activation of the extracellular signal-regulated kinase cascade or ternary complex formation at the fos serum response element promoter. The Wnt-mediated repression of c-Fos, FosB, and JunB expression was consistent with a decrease in their binding to an AP-1 promoter element and decreased target gene transcription. The expression of fos, fosB, junB, and egr1 was also repressed in human colon tumors relative to patient matched normal tissue. By contrast, the fos family member fra-1 was up-regulated in the human colon tumors, suggesting a compensatory mechanism for the reduction in fos and fosB expression. The results indicate that Wnt signaling can repress the expression of certain immediate early genes, and that this effect is consistent with changes in gene expression observed in human colorectal tumors.
Feature Selection with theBorutaPackage (2010)

This article describes a <b>R</b> package <b>Boruta</b>, implementing a novel feature selection algorithm for finding emph{all relevant variables}. The algorithm is designed as a wrapper around a Random Forest classification algorithm. It iteratively removes the features which are proved by a statistical test to be less relevant than random probes. The <b>Boruta</b> package provides a convenient interface to the algorithm. The short description of the algorithm and examples of its application are presented.
Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice (1994)

Targeted protein toxins are a new class of reagents with the potential for great tumor selectivity and cytotoxic potency. Two such compounds were studied: 1) Tf-CRM107, a conjugate of human transferrin (Tf) and diphtheria toxin with a point mutation (CRM107); and 2) 454A12-rRA, a conjugate of a monoclonal antibody (454A12) to the human Tf receptor and recombinant ricin A chain (rRA). Both compounds are potent and specific in killing human glioblastoma cell lines in vitro. The authors investigated the activity of these reagents administered intratumorally against solid U251 MG human gliomas in vivo. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were randomly assigned to be treated with 100-microliters intratumoral injections of Tf-CRM107 (10 micrograms) or 454A12-rRA (10 micrograms), equimolar doses of CRM107 (4.3 micrograms), 454A12 antibody (7.5 micrograms), or rRA (1.5 micrograms), or phosphate-buffered saline (PBS) every 2 days for a total of four doses. Tumor volume and animal weight were assessed by a blinded observer before each treatment and biweekly for 30 days after initiating therapy. With Tf-CRM107 administration, tumor regression of greater than 95% occurred by Day 14 (p < 0.01) and tumors did not recur by Day 30. Treatment with 454A12-rRA caused a 30% decrease in tumor volume by Day 14 (p < 0.01). Treatment with equimolar doses of the unconjugated targeted protein toxin components CRM107, 454A12, or rRA caused significant U251 MG tumor growth inhibition, but the effects were less potent than the antitumor effects of the conjugates. This study also characterized the dose-response effect of Tf-CRM107 on tumor growth and tumor weight on Day 30. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were treated with 100-microliters intratumoral injections of 10, 1.0, or 0.1 microgram of Tf-CRM107 or PBS every 2 days for a total of four doses. All three doses of Tf-CRM107 significantly inhibited tumor growth by Day 14 (p < 0.01) and at Day 30 (p < 0.05), with a significant dose-response relationship. This study demonstrated in vivo efficacy of the targeted toxins Tf-CRM107 and 454A12-rRA against a human glioma. With intratumoral administration, the effect of Tf-CRM107 was tumor-specific and in some animals curative. Regional therapy with these potent tumor-specific agents using direct intratumoral infusion should limit systemic toxicity and may be efficacious against brain tumors.
Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia (1989)

We have previously identified in the long control region of the genome of human papillomavirus type 16 (HPV-16) a DNA segment which functions as a cell-type-specific enhancer as well as mediating glucocorticoid response. It contains multiple transcription-factor-binding sites, including several for nuclear factor I and one for the glucocorticoid receptor, which binds to the partially palindromic sequence TGTACANNNTGTCAT. We report here that this sequence element, when separated from the surrounding transcription-factor-binding sites and placed as an oligonucleotide into a test vector, retains its function as a glucocorticoid response element (GRE) in HeLa cells. In T47D cells, which express the progesterone receptor, the HPV-16 enhancer fragment mediates progesterone responsiveness. A point mutant in this fragment and the response of the oligonucleotide clone to both steroids prove the identity of the progesterone response element (PRE) with the GRE. The antiprogesterone and antiglucocorticoid RU486 interferes with both hormonal responses. In SiHa cells, the HPV-16 GRE mediates an increase in transcripts encoding E6 and E7 proteins, which are involved in transformation by HPV-16. Hormonal regulation is not restricted to HPV-16: DNA segments containing the cell-type-specific enhancers of HPV-11 and HPV-18 also mediate glucocorticoid and progesterone response. We identified sequence elements in the long control regions of HPV-11 and HPV-18 which function as GRE/PREs when tested as oligonucleotides. These findings suggest that GRE/PREs are an integral part of gene expression regulation in genital HPVs.
Reliability, validity, and clinical correlates of apathy in Parkinson's disease (1992)

The authors examined a consecutive series of 50 patients for the presence of apathy, depression, anxiety, and neuropsychological deficits using a neuropsychological battery that included a recently designed apathy scale. This scale was found to be reliable and valid in the diagnosis of apathy in patients with PD. Of patients in the study, 12% showed apathy as their primary psychiatric problem, and 30% were both apathetic and depressed. Patients with apathy (with or without depression), showed significantly more deficits in both tasks of verbal memory and time-dependent tasks. Results suggest that apathy is a frequent finding in PD, is significantly associated with specific cognitive impairments, and may have a different mechanism than depression.
Reactive synchronization algorithms for multiprocessors (1994)

Synchronization algorithms that are efficient across a wide range of applications and operating conditions are hard to design because their performance depends on unpredictable run-time factors. The designer of a synchronization algorithm has a choice of protocols to use for implementing the synchronization operation. For example, candidate protocols for locks include test-and-set protocols and queueing protocols. Frequently, the best choice of protocols depends on the level of contention: previous research has shown that test-and-set protocols for locks outperform queueing protocols at low contention, while the opposite is true at high contention. This paper investigates reactive synchronization algorithms that dynamically choose protocols in response to the level of contention. We describe reactive algorithms for spin locks and fetch-and-op that choose among several shared-memory and message-passing protocols. Dynamically choosing protocols presents a challenge: a reactive algorithm needs to select and change protocols efficiently, and has to allow for the possibility that multiple processes may be executing different protocols at the same time. We describe the notion of consensus objects that the reactive algorithms use to preserve correctness in the face of dynamic protocol changes. Experimental measurements demonstrate that reactive algorithms perform close to the best static choice of protocols at all levels of contention. Furthermore, with mixed levels of contention, reactive algorithms outperform passive algorithms with fixed protocols, provided that contention levels do not change too frequently. Measurements of several parallel applications show that reactive algorithms result in modest performance gains for spin locks and significant gains for fetch-and-op.
Growth inhibition of clonogenic leukemic precursor cells by minor histocompatibility antigen-specific cytotoxic T lymphocytes. (1991)

Minor histocompatibility (mH) antigens appear to play a major role in bone marrow transplantation (BMT) using HLA-identical donors. Previously, we reported the isolation of major histocompatibility complex (MHC)-restricted mH antigen-specific cytotoxic T lymphocytes (CTL) from patients with graft-vs.-host disease or rejection after HLA-identical BMT. We have demonstrated that mH antigens can be recognized on hematopoietic progenitor cells, and residual recipient CTL specific for mH antigens expressed on donor hematopoietic progenitor cells may be responsible for graft rejection in spite of intensive conditioning regimens in HLA-identical BMT. Here, we investigated whether mH antigen-specific CTL directed against the mH antigens HA-1 to HA-5 and the male-specific antigen H-Y were capable of antigen-specific inhibition of in vitro growth of clonogenic leukemic precursor cells. We demonstrate that mH antigen-specific CTL against all mH antigens tested can lyse freshly obtained myeloid leukemic cells, that these mH antigen-specific CTL can inhibit their clonogenic leukemic growth in vitro, and that this recognition is MHC restricted. We illustrate that leukemic (precursor) cells can escape elimination by mH antigen-specific CTL by impaired expression of the relevant MHC restriction molecule. We suggest that mH antigen-specific MHC-restricted CTL may be involved in vivo in the graft-vs.-leukemia reactivity after BMT.
Can guava fruit intake decrease blood pressure and blood lipids? (1993)

A randomized, single-blind, controlled trial was conducted to examine the effects of guava fruit intake on BPs and blood lipids in patients with essential hypertension. Of 145 hypertensives that entered the trial, 72 patients were assigned to take a soluble fibre and a potassium-rich diet containing 0.5-1.0 kg of guava daily (group A) and 73 patients to their usual diet (group B), while salt, fat, cholesterol, caffeine and alcohol intake were similar in both groups. Mean age, mean body weight and male sex, were similar, and so were risk factors, mean BPs, mean serum sodium, potassium, calcium, magnesium, triglycerides, cholesterol and HDL-cholesterol in both groups. Dietary adherence to guava intake was checked by a questionnaire. After four weeks of follow-up on an increased consumption of dietary potassium and low sodium/potassium ratio, group A patients were associated with 7.5/8.5 mmHg net decrease in mean systolic and diastolic pressures compared with group B. Increased intake of soluble dietary fibre (47.8 +/- 11.5 vs. 9.5 +/- 0.85 g/day) was associated with a significant decrease in serum total cholesterol (7.9%), triglycerides (7.0%) and an insignificant increase in HDL-cholesterol (4.6%) with a mild increase in the ratio of total cholesterol/HDL-cholesterol in group A patients compared with group B. It is possible that an increased consumption of guava fruit can cause a substantial reduction in BPs and blood lipids with a lack of decrease in HDL-cholesterol due to its higher potassium and soluble fibre content, respectively.