Miracle-dz/UniFAR-FTUs huggingface dataset:
Histamine induced bronchoconstriction and end tidal inspiratory activity in man.

BACKGROUND: End tidal inspiratory activity (ETIA) in diaphragm and parasternal intercostal muscles can be evoked in man and in animals by administration of histamine. Exacerbations of asthma and administration of histamine are often accompanied by hyperinflation. The aims of the study were to determine (1) the magnitude of ETIA in response to histamine in man, (2) the relative contributions of chemical and mechanical stimulation of airway receptors to ETIA, and (3) the importance of ETIA to hyperinflation. METHODS: The effects of inhalation of histamine on the electrical activities of the diaphragm and parasternal intercostal muscles measured with surface electrodes were studied in 21 subjects. The experiments were repeated after inhalation of 600 micrograms of salbutamol to prevent histamine induced bronchoconstriction and concomitant mechanical stimulation of airway receptors. Subjects were connected to a closed breathing circuit to measure the changes in functional residual capacity (FRC) for the different experiments. RESULTS: The mean values of histamine induced ETIA were 60.6% and 46.9% of peak inspiratory activities during control conditions for the diaphragm and intercostal muscles, respectively. After salbutamol histamine induced ETIA was reduced to about one quarter of pre-salbutamol values. FRC increased by 427 ml as a result of inhalation of histamine, but after salbutamol this increase was only 53 ml. The data for ETIA and FRC were interpreted as indicating that the contributions of airflow limitation and ETIA to histamine induced hyperinflation are comparable. CONCLUSIONS: Histamine is a forceful stimulus for inducing ETIA. Both chemical and mechanical stimulation of airway receptors contribute to evoke ETIA, of which the contribution of mechanical stimulation is the more important one. ETIA contributes substantially to histamine induced hyperinflation.
Importance of Temporal Cues for Tactile Spatial- Frequency Discrimination

While scanning a textured surface with fingers, tactile information is encoded both spatially, by differential activation of adjacent receptors, and temporally, by changes in receptor activation during movements of the fingers across the surface. We used a tactile discrimination task to examine the dependence of human tactile perception on the availability of spatial and temporal cues. Subjects discriminated between spatial frequencies of metal gratings presented simultaneously to both hands. Tactile temporal cues were eliminated by preventing lateral hand movements; tactile spatial cues were eliminated by using gloves with an attached rubber pin. Analysis revealed separation of the subjects into two groups: “spatiotemporal” (ST) and “latent-temporal” (LT). Under normal conditions, the performance of ST subjects was significantly better than that of the LT subjects. Prevention of lateral movements impaired performance of both ST and LT subjects. However, when only temporal cues were available, the performance of ST subjects was significantly impaired, whereas that of the LT subjects either improved or did not change. Under the latter condition, LT subjects changed strategy to scanning with alternating hands, at velocities similar to the velocities normally used by ST subjects. These velocities generated temporal frequencies between 15 and 30 Hz. The LT subjects were unaware of their improved performance. Nine of ten LT subjects significantly improved their performance under normal conditions when trained to scan gratings using alternating hands and velocities similar to those used by ST subjects. We conclude that (1) temporal cues are essential for spatial-frequency discrimination, (2) human subjects vary in the tactile strategies they use for texture exploration, and (3) poor tactile performers can significantly improve by using strategies that emphasize temporal cues.
Biochemical Studies of Melibiose Metabolism in Wild Type and mel Mutant Strains of Salmonella typhimurium

I identified two enzyme activities, α-galactosidase and a galactoside permease, required for melibiose metabolism by Salmonella typhimurium. These activities are very low under normal growth conditions, but their production can be induced by melibiose and gratuitously by melibiitol. Melibiose induction is severely inhibited by glucose, but the glucose effect can be countered by 3′, 5′ cyclic adenosine monophosphate. I isolated two phenotypic classes of mutants not able to utilize melibiose as a carbon source. One class, Car−, is deficient in the phosphotransferase system. The other, Mel, lacks either α-galactosidase, galactoside permease, or both functions.
Optimization of Preference Queries with Multiple Constraints

Nowadays, the efficient integration of preference querying into standard database technology is an important issue. In some instances, preference queries challenge traditional query processing and optimization. In this paper we study preference database queries involving hard constraints over multiple attributes belonging to several relations. The main bottleneck for such queries is the computation of the cartesian product which may lead to high memory and computation costs. We develop algebraic optimization techniques to transform a preference query with hard constraints in order to enable its efficient processing by database engines. For this purpose, we show a dominance criterion and we introduce rewriting techniques to eliminate dominated tuples before building the cartesian product and therefore speed up the evaluation. These techniques lead to novel preference transformation laws and extend previous developed rules.
Adaptive Methods: Telling “The Rest of the Story”

The Food and Drug Administration (FDA) draft guidance on adaptive design randomized clinical trials provides in-depth consideration of the difficulties that unblinded adaptation of clinical trial design might introduce. We provide extended discussion of these difficulties, with focus on the problems that the adaptive designs pose in the scientific interpretation of randomized clinical trial results, for regulatory authorities as well as for patients and caregivers who wish to make evidence-based decisions regarding the choice of treatment. We consider implications in adequate and well-controlled studies of the use of unblinded measures of treatment effect to make adaptive selection/modification of treatments, adaptive selection of primary endpoints, adaptive modification of maximal sample size, adaptive modification of randomization ratios, and adaptive modification of target populations (adaptive enrichment), and then we consider the special topic of seamless phase 2–3 designs. We examine the extent to which the adaptive designs do not meet the goals of having greater efficiency, being more likely to identify truly effective treatments, being more informative, and providing greater flexibility. We fully support the FDA's continued requirement of adequate and well-controlled confirmatory studies, complete with prospective, detailed specification of the entire randomized clinical trial design in a way that allows accurate and precise estimation of treatment effectiveness.
Patient Radiation Dose in Diagnostic and Interventional Procedures for Intracranial Aneurysms: Experience at a Single Center

Objective To assess patient radiation doses during cerebral angiography and embolization of intracranial aneurysms in a large sample size from a single center. Materials and Methods We studied a sample of 439 diagnostic and 149 therapeutic procedures for intracranial aneurysms in 480 patients (331 females, 149 males; median age, 57 years; range, 21-88 years), which were performed in 2012 with a biplane unit. Parameters including fluoroscopic time, dose-area product (DAP), and total angiographic image frames were obtained and analyzed. Results Mean fluoroscopic time, total mean DAP, and total image frames were 12.6 minutes, 136.6 ± 44.8 Gy-cm2, and 251 ± 49 frames for diagnostic procedures, 52.9 minutes, 226.0 ± 129.2 Gy-cm2, and 241 frames for therapeutic procedures, and 52.2 minutes, 334.5 ± 184.6 Gy-cm2, and 408 frames for when both procedures were performed during the same session. The third quartiles for diagnostic reference levels (DRLs) were 14.0, 61.1, and 66.1 minutes for fluoroscopy time, 154.2, 272.8, and 393.8 Gy-cm2 for DAP, and 272, 276, and 535 for numbers of image frames in diagnostic, therapeutic, and both procedures in the same session, respectively. The proportions of fluoroscopy in DAP for the procedures were 11.4%, 50.5%, and 36.1%, respectively, for the three groups. The mean DAP for each 3-dimensional rotational angiographic acquisition was 19.2 ± 3.2 Gy-cm2. On average, rotational angiography was used 1.4 ± 0.6 times/session (range, 1-4; n = 580). Conclusion Radiation dose in our study as measured by DAP, fluoroscopy time and image frames did not differ significantly from other reported DRL studies for cerebral angiography, and DAP was lower with fewer angiographic image frames for embolization. A national registry of radiation-dose data is a necessary next step to refine the dose reference level.
Relationship Among Sexual Desire, Sexual Satisfaction, and Quality of Life in Middle-Aged and Older Adults

The authors examined the association among sexual desire, sexual satisfaction, and quality of life in a sample of community participants. They predicted that quality of life would be positivity correlated with sexual satisfaction and that sexual desire would indirectly influence quality of life. This research showed that elderly adults’ sexual desire and sexual satisfaction decrease with age and that nearly 40% of the interviewees still had sexual activity one or more times every month. The results revealed that sexual desire does not directly influence quality of life, but it does have a direct effect on sexual satisfaction; hence, sexual satisfaction will indirectly affect quality of life.
Nutrients and cardiovascular disease: no easy answers.

b-Carotene and cardiovascular disease illustrate a number of points. Good observational data suggested that diets high in fruit and vegetables were associated with lower risk of cardiovascular disease [1–3]. Limited animal work suggested that b-carotene, a nutrient found in abundance in fruits and vegetables, prevented lesion development [4]. The supposition was that b-carotene functioned as an antioxidant; hence, either alone or in combination with other antioxidants it would decrease the risk of developing cardiovascular disease. However, the outcome of intervention trials suggested that b-carotene had a null effect on the risk of developing cardiovascular disease and in susceptible individuals increased the risk of developing lung cancer, convincingly enough to halt concurrent interventions [5–7]. Using the smoke-exposed ferret as an animal model of lung cancer it was subsequently found that the oxidative breakdown products of b-carotene interfered with retinoid signaling, resulting in the formation of pre-cancerous (squamous metaplasia) lesions [8].
Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model.

BACKGROUND & AIMS One of the challenges to treating inflammatory bowel disease (IBD) is to target the site of inflammation. We engineered nanoparticles (NPs) to deliver an anti-inflammatory tripeptide Lys-Pro-Val (KPV) to the colon and assessed its therapeutic efficacy in a mouse model of colitis. METHODS NPs were synthesized by double-emulsion/solvent evaporation. KPV was loaded into the NPs during the first emulsion of the synthesis process. To target KPV to the colon, loaded NPs (NP-KPV) were encapsulated into a polysaccharide gel containing 2 polymers: alginate and chitosan. The effect of KPV-loaded NPs on inflammatory parameters was determined in vitro as well as in the dextran sodium sulfate-induced colitis mouse model. RESULTS NPs (400 nm) did not affect cell viability or barrier functions. A swelling degree study showed that alginate-chitosan hydrogel containing dextran-fluorescein isothiocyanate-labeled NPs collapsed in the colon. Once delivered, NPs quickly released KPV on or within the closed area of colonocytes. The inflammatory responses to lipopolysaccharide were reduced in Caco2-BBE (brush border enterocyte) cells exposed to NP-KPV compared with those exposed to NPs alone, in a dose-dependent fashion. Mice given dextran sodium sulfate (DSS) followed by NP-KPV were protected against inflammatory and histologic parameters, compared with mice given only DSS. CONCLUSIONS Nanoparticles are a versatile drug delivery system that can overcome physiologic barriers and target anti-inflammatory agents such as the peptide KPV to inflamed areas. By using NPs, KPV can be delivered at a concentration that is 12,000-fold lower than that of KPV in free solution, but with similar therapeutic efficacy. Administration of encapsulated drug-loaded NPs is a novel therapeutic approach for IBD.
The structure of obsessionality among young adults

Although the phenomenology of obsessive–compulsive disorder (OCD) is well understood, less is known about the structure of obsessive symptoms in non‐clinical populations. The present study examines the factorial structure of the Leyton Obsessional Inventory short form (LOI‐SF) in a sample of 1,015 undergraduate college students. Four factors were extracted describing concerns about contamination (labeled the Contamination factor); repeating behaviors or uncomfortable thoughts or doubts (labeled the Doubts/Repeating factor); checking behaviors, too much attention to detail, honesty concerns, strict conscience and strict routine (labeled the Checking/Detail factor); and taking a long time to dress and to hang up and put away clothing, as well as belief in extremely unlucky numbers (labeled Worries/Just Right factor). Self‐report measures of anxiety and ADHD symptoms were correlated positively with these factors, particularly with the checking/detail factor. The prevalence, symptom structure, and patterns of comorbidity seen in this sample of unselected college students are similar to the patterns seen in adolescents with OCD, suggesting that obsessional symptoms and OCD may exist along a continuum. Depression and Anxiety 20:77–85, 2004. © 2004 Wiley‐Liss, Inc.
Contributions to Colon Segmentation Without Previous Preparation in Computer Tomography Images

We propose a method to segment the lumen of the colon from computed tomography (CT) images. To do so, we use first and second order statistical moments. These moments provide us with a set of descriptors to characterize the homogeneity of regions inside the colon. The algorithm presented in this paper makes use of these values in a prediction-correction exploration process of the colonic region. We show some segmentation results on real patient images that present high nonhomogeneous colonic regions.
Prevalence of breastfeeding in the United States: the 2001 National Immunization Survey.

OBJECTIVE To address key gaps in the annual monitoring of breastfeeding prevalence in the United States, 3 breastfeeding questions concerning the initiation, duration, and exclusivity of breastfeeding were added to the rotating modules of the National Immunization Survey (NIS) beginning in the third quarter of 2001. The present study examines the current prevalence of breastfeeding in the United States using NIS data from this initial quarter. METHODS The NIS is a random-digit-dialing survey of households with children aged 19 to 35 months, followed by a mail survey of the eligible children's vaccination providers to validate the child's vaccination information. In the third quarter of 2001, a randomly selected subset of households interviewed in the NIS (N = 896) were asked questions about breastfeeding. RESULTS Almost two thirds (65.1%) of children had ever been breastfed. At 6 and 12 months, 27.0% and 12.3%, respectively, were receiving some breast milk. Non-Hispanic blacks had the lowest rates of breastfeeding initiation and continuation. Exclusive breastfeeding rates were low in the United States with only 7.9% at 6 months. CONCLUSIONS Although breastfeeding initiation is near the national goal of 75%, breastfeeding continuation lags behind the national goals of 50% and 25% at 6 and 12 months, respectively. Strenuous public health efforts are needed to improve breastfeeding practices among blacks.
Is resection indicated in gastric cancer deemed curable preoperatively but found to be advanced intraoperatively?

PURPOSE This study was designed to evaluate the value of resection and to analyze clinicopathologic data on gastric cancer patients who were evaluated as curable preoperatively but diagnosed as advanced intraoperatively. METHODS A retrospective analysis was performed on clinical, surgical, and pathological data of 264 patients who had undergone surgery for gastric cancer between January 2008 and October 2012. The patients who were diagnosed in advanced stages during surgical exploration were accepted into the study group. Patients were categorized into the following two groups: non-resection group (NRG) and resection group (RG). We compared the clinicopathologic features of the two groups and investigated the prognostic factors by performing univariate and multivariate analyses. RESULTS A total of 79 patients diagnosed with advanced disease in surgical exploration were evaluated. There were 40 patients (50.6%) in the NRG and 39 patients (49.4%) in the RG. The difference in median overall survival between the NRG and the RG was statistically significant (1.7 vs 5 months; p=0.001). In multivariate analysis, age less than 70 years, gastric resection, adjuvant chemotherapy, and male gender were found to be favorable significant independent prognostic factors for overall survival. CONCLUSION Resection seems to be associated with improved overall survival in patients who were diagnosed as advanced intraoperatively. Therefore, patient and tumor-related factors should be taken into consideration before planning resection. Randomized controlled studies are required.
Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein

Influenza A virus (IAV) defective RNAs are generated as byproducts of error-prone viral RNA replication. They are commonly derived from the larger segments of the viral genome and harbor deletions of various sizes resulting in the generation of replication incompatible viral particles. Furthermore, small subgenomic RNAs are known to be strong inducers of pattern recognition receptor RIG-I-dependent type I interferon (IFN) responses. The present study identifies a novel IAV-induced defective RNA derived from the PB2 segment of A/Thailand/1(KAN-1)/2004 (H5N1). It encodes a 10 kDa protein (PB2∆) sharing the N-terminal amino acid sequence of the parental PB2 protein followed by frame shift after internal deletion. PB2∆ induces the expression of IFNβ and IFN-stimulated genes by direct interaction with the cellular adapter protein MAVS, thereby reducing viral replication of IFN-sensitive viruses such as IAV or vesicular stomatitis virus. This induction of IFN is completely independent of the defective RNA itself that usually serves as pathogen-associated pattern and thus does not require the cytoplasmic sensor RIG-I. These data suggest that not only defective RNAs, but also some defective RNA-encoded proteins can act immunostimulatory. In this particular case, the KAN-1-induced defective RNA-encoded protein PB2∆ enhances the overwhelming immune response characteristic for highly pathogenic H5N1 viruses, leading to a more severe phenotype in vivo.
Mouse B lymphocyte specific endocytosis and recycling of MHC class II molecules.

In B lymphocytes, the processing of exogenous proteins and the subsequent binding of antigenic peptides to class II molecules encoded by the major histocompatibility complex (MHC) occurs most likely within endocytic compartments. To examine the endocytic transport of MHC class II molecules, we used (i) surface iodination followed by internalization, pronase treatment and immunoprecipitation, (ii) in situ iodination of endosomal compartments, and (iii) confocal microscopy to visualize the fate of fluorescence coupled Fab fragments. In murine I‐Ak, I‐Ek positive B lymphoma cells, cell surface MHC class II molecules are partially protected from pronase digestion after 15 min at 37 degrees C and recycled back to the cell surface within the next 30 min. The fluorescence coupled Fab fragments are delivered to juxtanuclear endocytic compartments in 15 min. In contrast to the murine B cells, L fibroblasts transfected with either I‐A alpha beta k or I‐E alpha k beta k,d fail to internalize their surface class II molecules. A fraction of class II molecules, however, is still present in endosomal compartments as detected after in situ iodination in L fibroblasts. We conclude that the recipient L fibroblasts lack one or several factors needed for the transport of MHC class II molecules from the cell surface to the endosomes. We suggest that in murine B lymphoma cells, antigenic peptides can gain access to a pool of recycling class II molecules whereas in L cells they meet newly synthesized class II molecules targeted to the endosomal compartments.
Sphingosine May Have Cytotoxic Effects via Apoptosis on the Growth of Keloid Fibroblasts

Keloids are often resistant to treatment, causing much suffering to the patient. Our previous work found that ceramide (Cer) inhibits growth of fibroblasts via apoptosis. However, when compared to normal fibroblasts (NFs), which are quiescent, keloid fibroblasts (KFs) rapidly proliferate and are reported to be resistant to apoptosis via Cer. Sphingosine (Sph) is a metabolite product of ceramide that has some different biochemical properties. Thereofore, we investigated the cytotoxic effects of Sph on cultured fibroblasts from keloid lesions and normal skin in order to evaluate the possibility of using Sph in the treatment of keloid. We used the lactic dehydrogenase (LDH) method, MTT method, and propidium iodide (PI) method. Sph had cytotoxic effects via apoptosis on both the KFs and NFs. Our results indicate that Sph may be applicable to the future treatment of keloid.
Amplification of Reiterated Sequences of Herpes Simplex Virus Type 1 (HSV-1) Genome To Discriminate between Clinical HSV-1 Isolates

ABSTRACT Herpes simplex virus type 1 (HSV-1)-related disease ranges from a localized, self-limiting illness to fatal disease in immunocompromised individuals. The corneal disease herpetic keratitis may develop after reactivation of a latent virus or reinfection with an exogenous herpesvirus. Molecular analysis of the virus involved may allow distinction between these two options. The HSV-1 genome contains several hypervariable regions that vary in numbers of reiterating regions (reiterations I to VIII [ReI to ReVIII]) between individual strains. Twenty-four HSV-1 clones, derived by subcloning of HSV-1 (strain F) twice in limiting dilutions, were tested in a PCR-based assay to analyze the stabilities of ReI, ReIII, ReIV, and ReVII. ReI and ReIII proved to vary in size upon subcloning, whereas ReIV and ReVII were stable. Subsequently, 37 unrelated isolates and 10 sequential isolates from five patients, all with HSV-1-induced keratitis, were genotyped for ReIV and ReVII. Of the 37 unrelated samples, 34 (92%) could be discriminated, while the genotypes of the viruses in sequential samples were identical for each individual. Conclusively, the data show that the approach presented allows the rapid and accurate discrimination of HSV-1 strains in studies that address the transmission and pathogenesis of HSV-1 infections.