Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of opioids on mechanosensitive pelvic nerve afferent fibers innervating the urinary bladder of the rat.

A total of 443 pelvic nerve afferent fibers in the L6 dorsal root of the rat were identified by electrical stimulation of the pelvic nerve; 319 (72%) were myelinated A delta fibers with a mean conduction velocity (CV) of 11.8 m/s and 124 (28%) were unmyelinated C fibers with mean CV of 1.9 m/s. Two hundred fifty-two fibers (57%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 108 were C fibers (mean CV; 1.9 m/s) and 144 were A delta fibers (mean CV; 8.2 m/s). Forty-nine UBD-sensitive fibers were further characterized; all gave monotonic increases in firing to increasing distending pressures. Thirty-six fibers (73%) had a low-threshold (LT) for response (mean: 6 mmHg) and 13 fibers (27%) had high-thresholds (HT) for response (mean: 32 mmHg). Responses of 15 fibers to graded UBD (11 LT and 4 HT) were tested before and after instillation of 0.5 ml of 30% xylenes (n = 11) or 5% mustard oil (n = 4) into the bladder. The mean resting activity of 13 fibers significantly increased, and 7 fibers exhibited sensitization of responses to graded UBD 30 min after xylenes or mustard oil instillation. All 4 HT fibers were sensitized; 3 of the 11 LT fibers were sensitized (i.e., gave increased responses to UBD). The effects of opioid receptor agonists were tested on responses to noxious UBD (80 mmHg). Cumulative intraarterial doses of mu-opioid receptor agonists (morphine, 8 mg/kg, and fentanyl, 300 micrograms/kg) and of delta-opioid receptor agonists (DPDPE, 300 micrograms/kg, and SNC-80, 300 micrograms/kg) did not affect responses to noxious UBD. In contrast, cumulative 16 mg/kg intraarterial doses of the kappa-opioid receptor agonists U50,488H, U69,593 and U62,066 dose-dependently attenuated responses to noxious UBD. There were no differences in the dose-response relationships of these drugs on afferent fibers from untreated and xylenes- or mustard oil-treated urinary bladder. These results reveal that there is a greater proportion of UBD-sensitive fibers in the L6 dorsal root (57%) than in the S1 dorsal root of the rat (38%; a previous study). The attenuation of responses to UBD by kappa, but not mu or delta opioid receptor agonists suggests a potential use for peripherally acting kappa opioid receptor agonists in the control of urinary bladder pain.
Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2‐specific antagonist is associated with reduced tumor growth

Neutrophils are important innate immune cells that are involved in microbial clearance at sites of infection and in wound healing. The microenvironment of tumors often resembles that of chronic inflammation and increased numbers of neutrophils have been observed in several tumors and, in some cases, these positively correlate with poor prognosis. Neutrophil recruitment into tumors appears to be dependent on chemokines that bind to CXCR1 and CXCR2 expressed by neutrophils. In our study, we used lung adenocarcinoma A549 multicellular tumor spheroids and A549 tumor xenografts along with a CXCR2‐specific small molecule inhibitor (AZ10397767) to investigate the recruitment and function of human neutrophils in tumors. We found that A549 spheroids constitutively secrete high levels of CXCL chemokines and that neutrophil recruitment into A549 tumors in vitro and in vivo is largely dependent on CXCR2 activation. AZ10397767 significantly reduced the numbers of infiltrating neutrophils into both in vitro and in vivo tumor models, which was associated with slower growing tumors. Neutrophil infiltration into A549 tumor spheroids increased their size compared to noninfiltrated spheroids and neutrophil‐derived factors increased the proliferation of A549 tumor cells and induced endothelial cell tubule formation in vitro. In contrast, we saw no reduction in microvascular density in AZ10397767‐treated A549 tumors or in tumors grown in CXCR2−/− mice, suggesting that angiogenesis in these tumors is CXCR2‐independent. Our data show that neutrophils can contribute to lung tumor growth and that CXCR2 antagonists may be a useful therapeutic agent in the treatment of lung carcinomas.
Emotion modulates cognitive flexibility in patients with major depression

Background Depression is associated with alterations of emotional and cognitive processing, and executive control in particular. Previous research has shown that depressed patients are impaired in their ability to shift attention from one emotional category to another, but whether this shifting deficit is more evident on emotional relative to non-emotional cognitive control tasks remains unclear. Method The performance of patients with major depressive disorder and matched healthy control participants was compared on neutral and emotional variants of a dynamic cognitive control task that requires participants to shift attention and response from one category to another. Results Relative to controls, depressed patients were impaired on both tasks, particularly in terms of performance accuracy. In the neutral go/no-go task, the ability of depressed patients to flexibly shift attention and response from one class of neutral stimuli to the other was unimpaired. This contrasted with findings for the emotional go/no-go task, where responding was slower specifically on blocks of trials that required participants to shift attention and response from one emotional category to the other. Conclusions The present data indicate that any depression-related difficulties with cognitive flexibility and control may be particularly evident on matched tasks that require processing of relevant emotional, rather than simply neutral, stimuli. The implications of these findings for our developing understanding of cognitive and emotional control processes in depression are discussed.
The Circadian Regulation of Presenilin‐2 Gene Expression

Circadian rhythms are generated by a molecular clock composed of clock genes and their protein products. Other genes are regulated in a rhythmic way by this molecular clockwork, but are not themselves constituents of the clock. This study shows that one of these clock‐controlled genes encodes the signalling protein Presenilin‐2. Indeed, evidence is presented that the promoter of the mouse Presenilin‐2 gene is bound and activated by CLOCK and BMAL1, transcription factors of the mammalian circadian clock. Quantification of Presenilin‐2 RNA shows that its expression is non‐rhythmic in many peripheral tissues (heart, muscle, kidney, spleen, and thymus). Note, though, that careful analysis of the liver data shows that Presenilin‐2 RNA exists in distinct isoforms in this tissue, and that rhythmicity is restricted to only a subset of these RNA isoforms. These data indicate a unique mode of regulation of Presenilin‐2 transcripts, the circadian control of which appears to happen at the transcriptional and post‐transcriptional levels.
Antibacterial Properties of Dental Luting Agents: Potential to Hinder the Development of Secondary Caries

A modified direct contact test was used to evaluate the antibacterial properties of four commercially available dental luting agents (RelyX Unicem, Ketac Cem, Ceramir Crown & Bridge and Harvard Cement) and two reference materials (glass-ionomer cement and calcium aluminate cement) compared to a negative-control material (PMMA). Streptococcus mutans bacteria were placed in direct contact with specimens that had been aged for 10 min, 1 day, and 7 days, in order to test the antibacterial properties of the materials. A metabolic assay containing resazurin was used to quantify the amount of viable bacteria remaining after the direct contact tests. The effects of pH and fluoride on bacteria proliferation were also evaluated. Strongest antibacterial properties were found for calcium aluminate cement, followed by Ceramir Crown & Bridge and RelyX Unicem. Ketac Cem, Harvard Cement, and the reference glass-ionomer cement showed bacteria content either higher than or not significantly different from the PMMA control in all instances. pH levels below 6.3 and above 9.0 were found to have negative effects on bacterial proliferation. No correlation between either acidic materials or fluoride release and antibacterial properties could be seen; rather, basic materials showed stronger antibacterial properties.
Language after section of the cerebral commissures.

SOME of the functional effects that appear in man following surgical separation of the hemispheres produced by complete transection of the corpus callosum plus the anterior and hippocampal commissures, with separation of the massa intermedia have been described in earlier reports (Gazzaniga, et al, 1962, 1963, 1965). The observations were based on two patients operated on by Drs. Philip Vogel and Joseph Bogen of the California College of Medicine at the White Memorial Medical Center in Los Angeles for relief of intractable seizures. In general the post-surgical studies indicate a striking functional independence of the gnostic activities of the two hemispheres. Perceptual, cognitive, mnemonic, learned and volitional activities persist in each hemisphere, but can proceed separately in each case outside the realm of awareness of the other hemisphere. The subjective experience of each hemisphere is known to the other only indirectly through lower level and peripheral effects.
Dynamic sealing ability of MTA root canal sealer.

AIMS To evaluate (i) the sealing ability of two sealers, mineral trioxide aggregate sealer (MTAS) and Pulp Canal Sealer (PCS), used with gutta-percha utilizing the fluid filtration method, (ii) leaching and surface characteristics in Hank's balanced salt solution (HBSS) over a period of time. METHODOLOGY Surface characteristics in HBSS were evaluated under the scanning electron microscope after 1 and 28 days, and the leaching of both sealers were assessed by inductively coupled plasma atomic absorption spectrometry (ICP-AAS). In addition, 24 single rooted extracted teeth were root filled using warm vertical compaction with either MTAS or PCS used as sealers with gutta-percha. Four teeth were used as positive and negative controls. Sealing ability was evaluated after 1 or 28 days using the fluid filtration method. RESULTS Mineral trioxide aggregate sealer exhibited crystalline deposits rich in calcium and phosphorus on its surface when in contact with a physiological solution. These crystalline deposits were absent in PCS and on MTAS stored at 100% humidity. The sealing ability of MTAS was similar to that of PCS. CONCLUSIONS The novel sealer based on mineral trioxide aggregate had comparable sealing ability to a proprietary brand sealer cement. In contact with a simulated body fluid, the MTA sealer released calcium ions in solution that encouraged the deposition of calcium phosphate crystals.
Expression of Keratinocyte Growth Factor in Goat Ovaries and Its Effects on Preantral Follicles Within Cultured Ovarian Cortex

The aims of this study were to evaluate the expression of keratinocyte growth factor (KGF) in goat ovaries and to study its effects on preantral follicle survival and development. The ovaries were used for immunohistochemistry or for in vitro culture for 1 or 7 days with KGF (0, 1, 10, 50, 100, 150, or 200 ng/mL). Noncultured (fresh control) and cultured ovarian slices were processed for histological analysis and transmission electron microscopy (TEM). The results showed that after 7 days of in vitro culture, all treatments had a significant reduction in the percentage of normal follicles compared with the fresh control. After 7 days of culture, the highest KGF concentrations (150 and 200 ng/mL) induced a significant reduction in the percentage of normal follicles compared with the tissues cultured in the absence (α-MEM+ alone) or presence of 1, 10, and 50 ng/mL KGF. Transmission electron microscopy confirmed follicular integrity after 7 days of culture in 1 ng/mL KGF. In addition, compared with the fresh control, the percentage of growing follicles was significantly increased in all treatments after 1 or 7 days of culture. Immunohistochemical analyses showed the expression of KGF in oocytes and granulosa cells in all follicle developmental stages as well as in thecal and stromal cells. In conclusion, this study demonstrated that, at the lowest concentration (1 ng/mL), KGF maintained the ultrastructure of goat preantral follicles cultured in vitro for up to 7 days. Furthermore, the KGF protein was widely distributed in goat ovaries, especially in ovarian follicles.
Classification, morphology and molecular pathology of premalignant lesions of the pancreas

Summary Over the past few years there have been substantial advances in our knowledge of premalignant lesions of the pancreas. Given the dismal prognosis of untreated pancreatic cancer, and the small proportion of patients who are operative candidates, an understanding of these premalignant lesions is essential for the development of strategies for early diagnosis and prevention. The 2010 WHO classification has added new entities, including intraductal tubular papillary neoplasms (ITPNs), and clarified the nomenclature and grading of previously recognised precursor lesions of pancreatic adenocarcinoma, such as intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and pancreatic intraepithelial neoplasia (PanIN). In particular, there has been an upsurge of interest in the natural history of IPMN, driven partly by improvements in imaging modalities and the consequent apparent increase in their incidence, and partly by recognition that subtypes based on location or histological appearance define groups with significantly different behaviours. In mid 2012 revised international guidelines for the classification and management of IPMNs and MCNs were published, although in several respects these guidelines represent a consensus view rather than being evidence-based. In recent years major advances in molecular technologies, including whole-exome sequencing, have significantly enhanced our knowledge of pancreatic premalignancy and have identified potentially highly specific diagnostic biomarkers such as mutations in GNAS and RNF43 that could be used to pre-operatively assess pancreatic cysts.
An Empirical Study of Open Source Software Usability: The Industrial Perspective

Recent years have seen a sharp increase in the use of open source projects by common novice users; Open Source Software OSS is thus no longer a reserved arena for software developers and computer gurus. Although user-centered designs are gaining popularity in OSS, usability is still not considered one of the prime objectives in many design scenarios. This paper analyzes industry users' perception of usability factors, including understandability, learnability, operability, and attractiveness on OSS usability. The research model of this empirical study establishes the relationship between the key usability factors and OSS usability from industrial perspective. In order to conduct the study, a data set of 105 industry users is included. The results of the empirical investigation indicate the significance of the key factors for OSS usability.
Decomposing a Chunk into Its Elements and Reorganizing Them As a New Chunk: The Two Different Sub-processes Underlying Insightful Chunk Decomposition

Familiar chunks can be processed highly efficiently, and this automatic process can prohibit the problem solver from developing novel and original ways to creatively solve difficult problems. For this reason, the role of the reverse process, chunk decomposition (CD), the process by which familiar patterns are broken down into their component elements in order to be regrouped in another meaningful manner, has been generally recognized as part of the creative process. However, previous studies on this issue have mainly focused on the decomposition process of CD (the D-process), while the reorganization process of CD has been greatly neglected or has not been distinctively identified in previous work. In this paper, we argue that the R-process could be equally as important as the D-process for CD. Even if a problem solver manages to decompose a familiar chunk into its elements, he or she still may not solve the problem if these elements are not successfully organized in a new and meaningful manner. To investigate whether the cognitive mechanism of the R-process is different from that of the D-process, we designed an experiment for detecting the effects of chunk tightness, which is regarded as the key factor in CD and which can be experimentally manipulated by the radical-level (loose) and stroke-level (tight) Chinese character CD tasks in the D-process, the R-process, and the more purified organization task (the O-process task) that does not involve the decomposition process. Our results showed that the stroke-level (tight) task was more difficult than the radical-level (loose) task for the D-process. However, for the R-process, the stroke- and radical-level tasks showed no differences in performance. Moreover, for the more purified reorganization task, the O-process task, the radical-level organization and reorganization could be even more difficult than the stroke-level organization and reorganization. This result demonstrated that the cognitive processes underlying chunk decomposition and reorganization are fundamentally different. Therefore, more general concepts such as chunk restructuring that could include both D- and R-processes might be more suitable in accounting for this type of creative insight.
Prime proportion affects masked priming of fixed and free-choice responses.

Left/right "fixed" responses to arrow targets are influenced by whether a masked arrow prime is congruent or incongruent with the required target response. Left/right "free-choice" responses on trials with ambiguous targets that are mixed among fixed trials are also influenced by masked arrow primes. We show that the magnitude of masked priming of both fixed and free-choice responses is greater when the proportion of fixed trials with congruent primes is . 8 rather than . 2. Unconscious manipulation of context can thus influence both fixed and free choices. Sequential trial analyses revealed that these effects of the overall prime context on fixed and free-choice priming can be modulated by the local context (i.e., the nature of the previous trial). Our results support accounts of masked priming that posit a memory-recruitment, activation, or decision process that is sensitive to aspects of both the local and global context.
Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder

Abstract Objective: This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD). Methods: Following a 6-week, open-label, dose-optimization period, children 6–12 years of age (n = 90) with ADHD were randomly assigned to double-blind MPH ERCT at the final optimized dose (20–60 mg/day) or placebo. After 1 week of double-blind treatment, efficacy was assessed predose and 0.75, 2, 4, 8, 10, 12, and 13 hours postdose in a laboratory classroom setting. The primary efficacy measure was the average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores, analyzed using a mixed-model, repeated-measures analysis. Secondary efficacy measures included Permanent Product Measure of Performance (PERMP) total number of problems attempted and total number of problems correct. Safety assessments included adverse event (AE) monitoring and the Columbia-Suicide Severity Rating Scale (C-SSRS). Results: MPH ERCT treatment statistically significantly reduced the average of all postdose SKAMP-Combined scores versus placebo (least-squares mean difference [95% confidence interval], −7.0 [−10.9, −3.1]; p < 0.001). Statistically significant treatment differences in SKAMP-Combined scores were observed at 2 hours postdose through 8 hours postdose (p-values <0.001). Statistically significant differences between MPH ERCT and placebo in PERMP total number of problems attempted and total number of problems correct were observed at 0.75 hours postdose through 8 hours postdose (p-values ≤0.049). Common AEs in the open-label period (≥5%) were decreased appetite, upper abdominal pain, mood swings, irritability, insomnia, upper respiratory tract infection (URTI), dysgeusia, and headache; URTI was the only AE reported by >1 subject receiving MPH ERCT in the double-blind period (placebo: URTI, contusion, wound, and initial insomnia). No suicidal ideation or behavior was reported on the C-SSRS at baseline or at any postbaseline assessment. Conclusions: MPH ERCT 20–60 mg significantly improved ADHD symptoms compared with placebo at 2 hours postdose through at least 8 hours postdose. MPH ERCT was generally safe and well tolerated, with a safety profile consistent with other MPH ER formulations. ClinicalTrials.gov Identifier: NCT01654250. www.clinicaltrials. gov/ct2/show/NCT01654250.
D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study.

UNLABELLED Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D(2) receptor availability by means of (123)I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug. METHODS Twenty-nine patients (19 men and 10 women, age range, 19-68 y) with schizophrenia treated with high doses (15 patients; 400-1,200 mg/d; mean dose, 666.7 +/- 219.3 mg/d) or low doses (14 patients; 50-300 mg/d; mean dose, 228.6 +/- 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of (123)I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang's first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background. RESULTS In all patients treated with amisulpride, specific binding of (123)I-IBZM to D(2) receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of (123)I-IBZM to dopamine D(2) receptors (0.20 vs. 0.31, P < 0.05). D(2) receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration. CONCLUSION Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D(2) receptors. The blockade of D(2) receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.
Development of the comprehensive observations of proprioception (COP): validity, reliability, and factor analysis.

OBJECTIVE We developed an observational tool, the Comprehensive Observations of Proprioception (COP), for identifying proprioceptive processing issues in children with developmental disabilities. METHOD Development of the COP underwent three phases. First, we developed items representing proprioceptive functions on the basis of an extensive literature review and consultation with occupational therapists. We then established interrater reliability and content, construct, and criterion validity. Finally, we completed a factor analysis of COP ratings of 130 children with known developmental disabilities. RESULTS Adequate validity and reliability were established. Factor analysis revealed a four-factor model that explained the underlying structure of the measure as it was hypothesized. CONCLUSION The COP is a valid criterion-referenced short observational tool that structures the clinician's observations by linking a child's behaviors to areas identified in the literature as relevant to proprioceptive processing. It takes 15 min to administer and can be used in a variety of contexts, such as the home, clinic, and school.