Miracle-dz/UniFAR-FTUs huggingface dataset:
A Single Intravesical Instillation of VAX014 Inhibits Orthotopic Superficial Bladder Tumor Implantation to Increase Survival.

BACKGROUND/AIM VAX014 minicells (VAX014) have been previously characterized as an integrin-specific oncolytic biotherapeutic agent. The present study was designed to evaluate the potential of VAX014 as an immediate post-operative intravesical adjuvant therapy in the treatment of non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS The ability of VAX014 to kill a panel of dissociated urothelial carcinoma cell lines was tested in vitro. In vivo experiments were conducted using a single intravesical dose of VAX014 in the anti-implantation variation of the MB49 syngeneic orthotopic bladder cancer model with tumor implantation and overall survival rates serving as study endpoints. RESULTS VAX014 rapidly killed dissociated urothelial carcinoma cells, while single dose in vivo pharmacology studies demonstrated the dose-dependent ability of VAX014 to prevent tumor implantation and development, ultimately resulting in a significant survival advantage compared to controls. CONCLUSION These results suggest that VAX014 holds potential as an immediate post-operative adjuvant therapy in NMIBC.
Effect of Intensive Salt‐Restriction Education on Clinic, Home, and Ambulatory Blood Pressure Levels in Treated Hypertensive Patients During a 3‐Month Education Period

The authors tested the hypothesis that low‐salt diet education by nutritionists would lower blood pressure (BP) levels in treated hypertensive patients. The amount of urinary salt excretion and clinic, home, and ambulatory BP values at baseline and at 3 months were measured in 95 patients with hypertension. After randomization to a nutritional education group (E group, n=51) or a control group (C group, n=44), the C group received conventional salt‐restriction education and the E group received intensive nutritional education aimed at salt restriction to 6 g/d by nutritionists. From baseline to the end of the study, 24‐hour urinary sodium excretion was significantly lowered in the E group compared with the C group (6.8±2.9 g/24 h vs 8.6±3.4 g/24 h, P<.01). Morning home systolic BP tended to be lowered in the E group (P=.051), and ambulatory 24‐hour systolic BP was significantly lowered in the E group (−4.5±1.3 mm Hg) compared with the C group (2.8±1.3 mm Hg, P<.001). Intensive nutritional education by nutritionists was shown to be effective in lowering BP in treated hypertensive patients.
Single-stranded structures are present within plasmids containing the Epstein-Barr virus latent origin of replication

The Epstein-Barr virus (EBV) latent origin of plasmid replication (oriP) contains two essential regions, a family of repeats with 20 imperfect copies of a 30-bp sequence and a dyad symmetry element with four similar 30-bp repeats. Each of the repeats has an internal palindromic sequence and can bind EBNA 1, a protein that together with oriP constitutes the only viral element necessary for EBV maintenance and replication. Using single-strand-specific nucleases, we have probed plasmids containing oriP-derived sequences for the presence of secondary structural elements. Multiple single-stranded structures were detected within the oriP region. Of the two essential elements of oriP, the family of repeats seemed to extrude these structures at a much higher frequency than did sequences within the dyad symmetry region. Though negative supercoiling was found to stabilize the single-stranded structures, they showed significant stability even after linearization of the oriP plasmids. Two major single-stranded structures detected involved approximately 12 bp of DNA. These loci could be transiently unwound regions that form because of negative supercoiling and the high A + T content of this region of DNA, or they could be cruciform structures extruded within the palindromic sequences of oriP that may be important sites for protein-DNA interactions in the EBV oriP.
A Review of Imaging Agent Development

This educational review highlights the processes, opportunities, and challenges encountered in the discovery and development of imaging agents, mainly positron emission tomography and single-photon emission computed tomography tracers. While the development of imaging agents parallels the drug development process, unique criteria are needed to identify opportunities for new agents. Imaging agent development has the flexibility to pursue functional or nonfunctional targets as long as they play a role in the specific disease or mechanism of interest and meet imageability requirements. However, their innovation is tempered by relatively small markets for diagnostic imaging agents, intellectual property challenges, radiolabeling constraints, and adequate target concentrations for imaging. At the same time, preclinical imaging is becoming a key translational tool for proof of mechanism and concept studies. Pharmaceutical and imaging industries face a common bottleneck in the form of the limited number of trials one company can possibly perform. However, microdosing and theranostics are evidence that partnerships between pharmaceutical and imaging companies can accelerate clinical translation of tracers and therapeutic interventions. This manuscript will comment on these aspects to provide an educational review of the discovery and development processes for imaging agents.
Oxysterols, but Not Cholesterol, Inhibit Human Immunodeficiency Virus Replication in Vitro

Oxysterols, oxygenated derivatives of cholesterol selected for their cytostatic activity and their inhibitory effect on cholesterol synthesis, have been investigated for their anti-human immunodeficiency virus (HIV) activity in vitro. The three oxysterols tested, 7β-hydroxycholesterol (7β-OHC), 25-hydroxycholesterol (25-OHC) and 7β,25-dihydroxycholesterol (7,25-OHC), inhibit viral replication at micromolar concentrations. The selectivity indexes for 7β-OHC and 25-OHC are quite modest (2 to 8) but reproducible; the dihydroxycholesterol 7,25-OHC exhibited antiviral properties at concentrations 13- to 25-fold lower than the highest concentration tested at which no toxicity was measurable. Oxysterols are naturally occurring compounds, and we speculate on their physiological relevance in HIV-infected individuals.
Effet des vitesses de dessiccation de la graine et des basses températures sur la germination du pois protéagineux

Des semis precoces permettent d'allonger les cycles de culture du pois proteagineux et d'eviter les stress hydriques et thermiques tardifs, ce qui contribue a la maitrise des variations de rendement. Les objectifs de ce travail sont 1) d'etudier le comportement de differents genotypes de pois au cours de la germination en reponse a la temperature ; 2) de determiner l'impact des vitesses de dessiccation a temperature elevee sur les caracteristiques des graines, leur germination et leur conservation ; 3) d'explorer la reprise du metabolisme energetique et la mobilisation des sucres solubles au cours de la germination et de determiner l'impact d'une vitesse de dessiccation rapide apres la phase de remplissage et des basses temperatures pendant la germination. Les pois de printemps Baccara et Terese et le pois d'hiver Champagne presentent une temperature de base identique et tres basse de -1,1°C. Le genotype Champagne a une vitesse de germination plus rapide que les deux autres genotypes, des basses temperatures jusqu'a l'optimum. Les vitesses de dessiccation elevees ont peu d'impact sur la germination mais affectent fortement l'aptitude a la conservation des graines, mesuree apres deterioration controlee. Cela est associe a une augmentation de la conductivite traduisant des degâts cellulaires, en particulier au niveau des membranes. La vitesse elevee de germination de Champagne s'explique en partie par une grande vitesse d'imbibition, permettant une respiration plus forte. Une correlation entre la consommation en oxygene et la production d'ATP a ete trouvee. Champagne presente egalement une capacite de la voie alternative, une utilisation d'ATP et de sucres solubles plus elevees que les genotypes de printemps, Baccara et Terese. L'utilisation des sucres solubles des axes embryonnaires, apres mobilisation des RFO, est bien correlee avec la vitesse de germination. De fortes vitesses de dessiccation entrainent une augmentation de la respiration qui serait a relier a la mise en place de mecanismes de reparation. Les basses temperatures retardent le processus de germination et de reprise du metabolisme par leur action sur les systemes enzymatiques, mais lorsque l'echelle de temps est exprimee en temps thermique, le retard disparait. Cependant, la respiration du genotype Champagne est moins affectee par les basses temperatures. Les resultats obtenus ont permis de proposer un schema global resumant les etapes cles permettant une vitesse de germination rapide et un modelesur le role de l'adenylate kinase et de la phosphorylation oxydative mitochondriale dans la regulation du metabolisme en lien avec l'anhydrobiose.
A 78 kDa glucose-regulated protein gene of Spirometra erinacei plerocercoid induced by chemical and physiological stresses

To adapt to different environmental conditions between poikilothermic and homeothermic hosts, the plerocercoid of Spirometra erinacei (sparganum) might express a variety of biologically active molecules. We have identified a 78 kDa glucose-regulated protein of the sparganum (SpGrp78) by differential display of mRNA, employing RNAs each from sparganum adjusted at 9 °C and 37 °C. A full-length cDNA of 2148 bp encodes for a protein of 651 amino acids with a predicted molecular mass of 71 610 Da and shares molecular characteristics with heat-shock protein 70, including a putative ATP binding site, signal peptide cleavage site and endoplasmic reticulum retention signal. Phylogenetic analysis revealed that SpGrp78 was mostly related to those of Echinococcus multilocularis and E. granulosus. Expression of SpGrp78 mRNA increased approximately 7-fold by inhibition of glycosylation by tunicamycin, 2-fold by temperature-shift from 9 °C to 37 °C and slightly by pH-shift to 4·0 or 5·5. These results suggested that induction of SpGrp78 mRNA is related to the functional role of SpGrp78 as a molecular chaperone when the parasite adapts to a new host environment.
Partitioning Patches into Test-equivalence Classes for Scaling Program Repair

Automated program repair is a problem of finding a transformation (called a patch) of a given incorrect program that eliminates the observable failures. It has important applications such as providing debugging aids, automatically grading assignments and patching security vulnerabilities. A common challenge faced by all existing repair techniques is scalability to large patch spaces, since there are many candidate patches that these techniques explicitly or implicitly consider. The correctness criterion for program repair is often given as a suite of tests, since a formal specification of the intended program behavior may not be available. Current repair techniques do not scale due to the large number of test executions performed by the underlying search algorithms. We address this problem by introducing a methodology of patch generation based on a test-equivalence relation (if two programs are "test-equivalent" for a given test, they produce indistinguishable results on this test). We propose two test-equivalence relations based on runtime values and dependencies respectively and present an algorithm that performs on-the-fly partitioning of patches into test-equivalence classes. Our experiments on real-world programs reveal that the proposed methodology drastically reduces the number of test executions and therefore provides an order of magnitude efficiency improvement over existing repair techniques, without sacrificing patch quality.
Depletion of Mutant p 53 and Cytotoxicity of Histone Deacetylase Inhibitors

Mutant p53 is a cancer-specific target for pharmacologic intervention. We show that histone deacetylase inhibitors such as FR901228 and trichostatin A completely depleted mutant p53 in cancer cell lines. This depletion was preceded by induction of p53-regulated transcription. In cells with mutant p53 pretreated with histone deacetylase inhibitors, DNA damage further enhanced the p53 trans-function. Furthermore, histone deacetylase inhibitors were preferentially cytotoxic to cells with mutant p53 rather than to cells lacking wild-type p53. We suggest that, by either restoring or mimicking p53 trans-functions, histone deacetylase inhibitors initiate degradation of mutant p53. Because mutant p53 is highly expressed, a sudden restoration of p53-like functions is highly cytotoxic to cells with mutant p53. In a broader perspective, this shows how selectivity may be achieved by targeting a non-cancer-specific target, such as histone deacetylases, in the presence of a cancer-specific alteration, such as mutant p53. (Cancer Res 2005; 65(16): 7386-92)
Inhibiting early activation of tissue nuclear factor-kappa B and nuclear factor interleukin 6 with (1-->3)-beta-D-glucan increases long-term survival in polymicrobial sepsis.

BACKGROUND Recent data implicate the activation of nuclear factor-kappa B (NF-kappa B) and nuclear factor interleukin 6 (NF-IL6) as important steps in the pathophysiologic mechanisms of adult respiratory distress syndrome and systemic inflammatory response syndrome. METHODS This study evaluated the effect of immunomodulating polysaccharides on transcription factor activation, cytokine expression, and mortality in a murine cecal ligation and puncture (CLP) model. ICR/HSD mice were treated with glucan (50 mg/kg) 1 hour before or 15 minutes after CLP. Liver and lung tissue were harvested at 3 hours and mortality trends were observed for 20 days. RESULTS CLP increased liver and lung NF-kappa B and NF-IL6 nuclear binding activity as well as tumor necrosis factor-alpha and interleukin 6 messenger RNA levels at 3 hours. Pretreatment or posttreatment with glucans inhibited tissue NF-kappa B and NF-IL6 nuclear binding activity and tissue cytokine messenger RNA levels. Prophylaxis with glucan phosphate or scleroglucan increased (P < .001) long-term survival (20% CLP vs 65% glucan phosphate, 75% scleroglucan). Posttreatment with glucan phosphate also increased (P < .05) long-term survival (20% vs 65%). CONCLUSIONS Pretreatment or posttreatment with biologic response modifiers decreased tissue transcription factor nuclear binding activity and cytokine message in liver and lung of septic mice. Inhibiting early transcription factor activation and cytokine message expression correlates with improved outcome in polymicrobial sepsis as denoted by increased long-term survival.
Seton treatment of anal fistula: experience with a new modification.

OBJECTIVE To describe a modified method of seton treatment of anal fistula. DESIGN Retrospective study. SETTING Teaching hospital, Poland. SUBJECTS 33 patients operated on for anal fistulas between January 1992 and September 1996. INTERVENTIONS A modified seton technique in which a rubber band was pulled through fistulous track and tightened around the external sphincter by a thread tied around its ends. MAIN OUTCOME MEASURES Anal incontinence, fistula recurrences. RESULTS Of the 33 patients, 22 had high trans-sphincteric, 4 had suprasphincteric, and 7 had extrasphincteric fistulas. No fistula recurred. All patients were sent a questionnaire and 32 replied (97%). 26 patients had normal control of solid stool. I was incontinent less than once a week, and 5 less than once a month. 20 patients were continent to liquid stool. 3 patients experienced problems controlling liquid stool less than once a week, and 9 less than once a month. 21 patients had normal control of flatus. 9 experienced minor soiling. CONCLUSION The method is simple, therapeutic results are satisfactory, and patients tolerate the procedure well. We recommend it in any case in which total fistulectomy cannot be done because of the risk of incontinence.
An ICF-CY-based approach to assessing self- and observer-reported functioning in young persons with achondroplasia – development of the pilot version of the Achondroplasia Personal Life Experience Scale (APLES)

Abstract Purpose: Achondroplasia is the most common disproportionate short stature which impacts patients’ well-being. Little is known about the burden of disease in terms of functioning of patients and few disease-specific patient-reported outcome (PRO) measures exist. To understand the consequences of achondroplasia, the objective of the study was to develop an achondroplasia-specific PRO tool. Method: Focus group discussions including 34 German patients (age 8–18 years) and 21 parents were conducted and qualitatively analyzed. To identify relevant concepts, statements were coded according to the International Classification of Functioning, Disability and Health: Children & Youth version (ICF-CY). Upon condensation, relevant statements were reformulated as items. Results: 1950 statements related to 125 ICF-CY categories were identified. After condensation and prioritization, 59 items were retained. These were generated based on the ICF-CY domains environmental factors (27 items), activities and participation (18 items), body functions (9 items), and body structures (5 items). Conclusions: A new instrument, the Achondroplasia Personal Life Experience Scale (APLES) to assess burden of disease and functioning from the patients perspective of children and adolescents with achondroplasia has been developed in its pilot version based on the classification of the ICF-CY. Psychometric performance of the APLES is currently being examined. Implications for Rehabilitation Using the ICF-CY within the development of a disease-specific instrument to assess burden of disease and functioning provides guidance for clinicians and researchers in the selection of appropriate instruments complying with ICF categories. Qualitative research based on focus group interviews is an effective method to elicit experiences, beliefs, points of view, understandings, perceptions, impressions, needs and concerns as well as attitudes from the perspective of the individuals on a specific topic such as functioning. Direct assessment of the patient perspective is necessary to thoroughly understand a patient’s experience of disease and treatment, the impact on their functioning and relevant health-care needs. Including the perspective of the patient and its family is an important component in the provision of health-care services. Patient-reported outcomes are not only important for the development of interventions and the use in clinical trials but can also be used in medical decision-making processes.
Examining the Correlates of Women’s Use of Sexual Coercion

Research in the last few years has begun to examine the prevalence of female sexual offending as well as attempting to understand the predictors of sexually coercive behavior among women. Although women engage in sexual coercion significantly less often than men, more research on female sexual coercion is warranted. The current study provides an exploratory examination of the relationship between several attitudinal, experiential, and situational factors, and the use of various sexual coercion tactics among a sample of 582 sexually active, female undergraduate students, as well as proposing an explanatory model of female sexual coercion. Results indicate that several variables that are significant predictors of sexual aggression for men are also predictive for women. However, these variables seem to work differently in predicting sexually coercive behavior for women. Implications for theory and further study are discussed.
A modified model of graft-versus-host-induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease.

OBJECTIVE Diffuse systemic sclerosis (SSc; scleroderma) is a debilitating disease characterized by excessive dermal fibrosis with later progression to internal organs. In addition to the fibrotic component, major aspects of the disease include vascular or circulatory involvement and immune dysregulation evidenced by inflammatory cells in affected tissues and production of autoantibodies. Many animal models resembling this disease have been studied, including genetic models in mice and chickens, challenge with chemicals such as bleomycin or vinyl chloride to induce fibrosis, and models of graft-versus-host (GVH)-induced disease using certain strains of mice with differences in minor histocompatibility loci. The present studies were undertaken to determine if alteration of the induction of GVH-induced scleroderma could result in a model that more fully represented the human condition. METHODS Disease was induced by injection of spleen cells from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination-activating gene 2 targeted). Dermal thickening, collagen deposition, vasoconstriction, and parameters of immunity were analyzed. RESULTS Similar to the human disease, this modified GVH model of SSc demonstrated evidence of dermal thickening, particularly in the extremities, progressive fibrosis of internal organs, vasoconstriction and altered expression of vascularity markers in skin and internal organs, early immune activation, inflammation in skin and internal organs, and autoantibody generation. CONCLUSION This modified model of GVH-induced SSc exhibits all major components of human disease and is likely to contribute to better understanding of the disease mechanisms and, ultimately, improved treatments for patients.
Nitric oxide‐mediated augmentation of neutrophil reactive oxygen and nitrogen species formation: Critical use of probes

Previous reports from this laboratory and others demonstrated NO‐mediated biphasic modulation of NADPH oxidase and attenuation of neutrophil reactive oxygen species generation, whereas recently we reported augmentation in DCF fluorescence following NO treatment. These discrepancies seem to be due to utilization of different probes/methods to assess effect of NO on reactive oxygen and nitrogen species (ROS/RNS, reactive species) generation. This study aims to look into this and evaluate NO‐mediated enzymatic reactive species formation by using multiple probes, human neutrophils/HL60 cells and various interventions. Addition of NO donor, SNP or SNAP (100 nM–1 mM) to PMNs suspension, exhibited a concentration‐ and time‐dependent augmentation in DCF fluorescence, but reduced DHE fluorescence. Collective generation of reactive species was confirmed by enhanced DMPO‐nitrone adduct, dityrosine and rhodamine‐123 and quenching of scopoletin. NO also enhanced bacterial killing, without altering phagocytosis. Addition of NO to HL‐60 cells lacking functional NADPH oxidase enhanced reactive species formation, indicating importance of other enzyme(s) too. NO‐dependent ROS/RNS generation was substantially reduced by NADPH oxidase inhibitor (DPI), MPO inhibitor (ABAH), or NOS inhibitor (7‐NI). However, 7‐NI reduced MPO activity, warranting reappraisal of those reports, which implied NOS in reactive species formation. The results obtained demonstrated NO‐mediated reactive species augmentation in human PMNs. Furthermore, superoxide scavenging by NO seems to be the key process in the decrease of DHE fluorescence and suggest usefulness of DCF as the most appropriate probe to measure the NO‐mediated modulation of reactive oxygen species in particular in various pathological situations. © 2010 International Society for Advancement of Cytometry
Remote-sensing issues for intelligent underwater systems

For certain applications an autonomous underwater system may benefit from a perception of its environment in terms of magnetics, gravity, chemical signature, or other sensing modalities. An introduction is presented for researchers unfamiliar with issues in underwater remote sensing. Application areas include machine perception for intelligent underwater systems, large-scale seafloor mapping, survey, and environmental characterization. <<ETX>>