Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-associated increase in salt sensitivity is accompanied by a shift in the atrial natriuretic peptide modulation of the effect of marinobufagenin on renal and vascular sodium pump

Background: Marinobufagenin (MBG) promotes natriuresis via inhibition of renotubular Na/K-ATPase (NKA) and causes vasoconstriction via inhibition of vascular NKA. Atrial natriuretic peptide (ANP), via cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)-dependent mechanism, sensitizes renal NKA to MBG but reduces MBG-induced inhibition of vascular NKA. As aging is associated with a downregulation of cGMP/PKG signaling, we hypothesized that in older rats, ANP would not potentiate renal effects of MBG and would not oppose vascular effects of MBG. Methods: In younger (3-month-old) and older (12-month-old) Sprague–Dawley rats, we compared SBP, natriuresis, activity of NKA in aorta and renal medulla, and levels of MBG and &agr;-ANP at baseline and following acute NaCl loading (20%, 2.5 ml/kg, intraperitoneally), and studied modulation of MBG-induced NKA inhibition by &agr;-ANP in vitro. Results: As compared with younger rats, NaCl-loaded older rats exhibited a greater MBG response, greater SBP elevation (25 vs. 10 mmHg, P < 0.01) and greater inhibition of NKA in aorta (39 vs. 7%, P < 0.01), 30% less natriuresis, and less inhibition of renal NKA (25 vs. 42%, P < 0.05) in the presence of comparable responses of &agr;-ANP and cGMP. In aorta and kidney of older rats, the levels of PKG were reduced, the levels of phosphodiesterase-5 were increased compared with that in young rats, and &agr;-ANP failed to modulate MBG-induced NKA inhibition. Conclusion: Age-associated downregulation of cGMP/PKG-dependent signaling impairs the ability of ANP to modulate the effects of MBG on the sodium pump, which contributes to salt sensitivity.
Information technology and social sciences: how can health IT be used to support the health professional?

Keeping up to date with the increasing amount of health‐related knowledge and managing the increasing numbers of patients with more complex clinical problems is a challenge for healthcare professionals and healthcare systems. Health IT applications, such as electronic health records or decision‐support systems, are meant to support both professionals and their support systems. However, for physicians using these applications, the applications often cause new problems, such as the impracticality of their use in clinical practice. This review adopts a social sciences perspective to understand these problems and derive suggestions for further development. Indeed, humans use tools to remediate the brain's weaknesses and enhance thinking. Available health IT tools have been shaped to fit administrative needs rather than physicians’ needs. To increase the beneficial effect of health IT applications in health care, clinicians’ style of thinking and their learning needs must be considered when designing and implementing such systems. New health IT tools must be shaped to fit health professionals’ needs. To further ease the integration of new health IT tools into clinical practice, we must also consider the effects of implementing new tools on the wider social framework.
CpG DNA as a vaccine adjuvant

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimized by maintaining ODNs and vaccine in close proximity. The adjuvant properties of CpG ODNs are observed when administered either systemically or mucosally, and persist in immunocompromised hosts. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer. Clinical trials demonstrate that CpG ODNs have a good safety profile and increase the immunogenicity of coadministered vaccines.
The effect of high performance gradients on fast gradient echo imaging

The effect of gradient system performance on segmented k‐space gradient echo imaging is presented. Three cases were investigated. First, an ideal system that has infinite slew rates and unlimited maximum gradient strengths was considered. Second, a “high speed” imaging system (2.3 (G/cm), 23 (G/cm)/ms) was considered. These two cases were compared with a “conventional” imaging system (1(G/cm), 1.67 (G/cm)/ms). It was found that substantial increases in SNR can be achieved (≈︁ 45%) by using high speed versus a conventional gradient system, for a TR of 6 ms. For trapezoidal gradient waveforms, there exists an optimum maximum gradient strength for a given slew rate, and any increase in gradient strength above this optimum will not be utilized by an optimized sequence. These studies have shown that increasing TR without decreasing the bandwidth is not a good way to increase SNR for constant scan time.
Identification of intragenic deletions and duplication in the FLCN gene in Birt‐Hogg‐Dubé syndrome

Birt‐Hogg‐Dubé syndrome (BHDS), caused by germline mutations in the folliculin (FLCN) gene, predisposes individuals to develop fibrofolliculomas, pulmonary cysts, spontaneous pneumothoraces, and kidney cancer. The FLCN mutation detection rate by bidirectional DNA sequencing in the National Cancer Institute BHDS cohort was 88%. To determine if germline FLCN intragenic deletions/duplications were responsible for BHDS in families lacking FLCN sequence alterations, 23 individuals from 15 unrelated families with clinically confirmed BHDS but no sequence variations were analyzed by real‐time quantitative PCR (RQ‐PCR) using primers for all 14 exons. Multiplex ligation‐dependent probe amplification (MLPA) assay and array‐based comparative genomic hybridization (aCGH) were utilized to confirm and fine map the rearrangements. Long‐range PCR followed by DNA sequencing was used to define the breakpoints. We identified six unique intragenic deletions in nine patients from six different BHDS families including four involving exon 1, one that spanned exons 2–5, and one that encompassed exons 7–14 of FLCN. Four of the six deletion breakpoints were mapped, revealing deletions ranging from 5688 to 9189 bp. In addition, one 1341 bp duplication, which included exons 10 and 11, was identified and mapped. This report confirms that large intragenic FLCN deletions can cause BHDS and documents the first large intragenic FLCN duplication in a BHDS patient. Additionally, we identified a deletion “hot spot” in the 5′‐noncoding‐exon 1 region that contains the putative FLCN promoter based on a luciferase reporter assay. RQ‐PCR, MLPA and aCGH may be used for clinical molecular diagnosis of BHDS in patients who are FLCN mutation‐negative by DNA sequencing. Published 2011 Wiley‐Liss, Inc.
Overexpression of Cyclooxygenase-2 in Rat Oral Cancers and Prevention of Oral Carcinogenesis in Rats by Selective and Nonselective COX Inhibitors

Oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide (NQO) show substantial overexpression of cyclooxygenase-2 (COX-2) when compared with adjacent phenotypically normal oral tissues. By contrast, neither 5-lipoxygenase (LOX) nor 12-LOX is overexpressed in rat oral cancers. Two chemoprevention studies were done to test the resulting hypothesis that COX-2 is a useful target for oral cancer chemoprevention in the rat. In both studies, male F344 rats received drinking water exposure to NQO (20 ppm) for 10 weeks, followed by administration of chemopreventive agents from week 10 until study termination at week 26. In the first study, groups of rats were fed basal diet (control), or basal diet supplemented with the selective COX-2 inhibitor celecoxib (500 or 1,500 mg/kg diet), the nonselective COX inhibitor piroxicam (50 or 150 mg/kg diet), or the 5-LOX inhibitor zileuton (2,000 mg/kg diet). In the second study, rats were fed basal diet (control) or basal diet supplemented with nitric oxide–naproxen (180 or 90 mg/kg diet), a nonselective COX inhibitor that shows reduced gastrointestinal toxicity. When compared with dietary controls, celecoxib decreased oral cancer incidence, cancer invasion score, and cancer-related mortality. Piroxicam decreased cancer-related mortality and cancer invasion score, whereas nitric oxide–naproxen decreased oral cancer incidence and cancer invasion score. By contrast, zileuton showed no chemopreventive activity by any parameter assessed. These data show that both selective and nonselective inhibitors of COX-2 can prevent NQO-induced oral carcinogenesis in rats. The chemopreventive activity of COX inhibitors may be linked to overexpression of their enzymatic target in incipient oral neoplasms. Cancer Prev Res; 3(1); 73–81.
Similar expression profiles in CD34+ cells from chronic phase chronic myeloid leukemia patients with and without deep molecular responses to nilotinib

The life expectancy of patients with chronic phase chronic myeloid leukemia on tyrosine kinase inhibitor therapy now approaches that of the general population. Approximately 60% of patients treated with second generation tyrosine kinase inhibitors achieve a deep molecular response, the prerequisite for a trial of treatment-free remission. Those patients unlikely to achieve deep molecular response may benefit from more intensive therapy up front. To identify biomarkers predicting deep molecular response we performed transcriptional profiling on CD34+ progenitor cells from newly diagnosed chronic phase chronic myeloid leukemia patients treated with nilotinib on a prospective clinical trial. Using unsupervised and targeted analytical strategies, we show that gene expression profiles are similar in patients with and without subsequent deep molecular response. This result is in contrast to the distinct expression signature of CD34+ chronic phase chronic myeloid leukemia patients failing to achieve a cytogenetic response on imatinib and suggests that deep molecular response to second-generation tyrosine kinase inhibitors is governed by the biology of more primitive chronic myeloid leukemia cells or extrinsic factors.
DNA methylation‐mediated silencing of nonsteroidal anti‐inflammatory drug‐activated gene (NAG‐1/GDF15) in glioma cell lines

Nonsteroidal anti‐inflammatory drug‐activated gene, NAG‐1, a transforming growth factor‐β member, is involved in tumor progression and development. The association between NAG‐1 expression and development and progression of glioma has not been well defined. Glioblastoma cell lines have lower basal expression of NAG‐1 than other gliomas and normal astrocytes. Most primary human gliomas have very low levels of NAG‐1 expression. NAG‐1 basal expression appeared to inversely correlate with tumor grade in glioma. Aberrant promoter hypermethylation is a common mechanism for silencing of tumor suppressor genes in cancer cells. In glioblastoma cell lines, NAG‐1 expression was increased by the demethylating agent, 5‐aza‐2′‐deoxycytidine. To investigate whether the NAG‐1 gene was silenced by hypermethylation in glioblastoma, we examined DNA methylation status using genomic bisulfite sequencing. The NAG‐1 promoter was densely methylated in several glioblastoma cell lines as well as in primary oligodendroglioma tumor samples, which have low basal expression of NAG‐1. DNA methylation at two specific sites (−53 and +55 CpG sites) in the NAG‐1 promoter was strongly associated with low NAG‐1 expression. The methylation of the NAG‐1 promoter at the −53 site blocks Egr‐1 binding and thereby suppresses Nag‐1 induction. Treatment of cells with low basal NAG‐1 expression with NAG‐1 inducer also did not increase NAG‐1. Incubation with a demethylation chemical increased Nag‐1 basal expression and subsequent incubation with a NAG‐1 inducer increased NAG‐1 expression. We concluded from these data that methylation of specific promoter sequences causes transcriptional silencing of the NAG‐1 locus in glioma and may ultimately contribute to tumor progression.
Steroid-sparing effects of pentoxifylline in pulmonary sarcoidosis.

BACKGROUND Agents that target pro-inflammatory cytokines may be useful in pulmonary sarcoidosis. OBJECTIVE To determine effectiveness of a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor, pentoxifylline (POF). DESIGN Randomized, double-blind, placebo-controlled trial, SETTING Clinical Research Center, National Institutes of Health. PATIENTS 27 patients with biopsy-confirmed pulmonary sarcoidosis receiving prednisone. INTERVENTION Placebo or POF (1200-2000 mg/day) for 10 months, as prednisone was tapered. MEASUREMENTS Primary endpoints: sustained improvement in two or more pulmonary function parameters, or a combination of one pulmonary function parameter and dyspnea. RESULTS Except for one patient, primary endpoints were not reached in POF-treated patients. Therefore, a post hoc analysis was performed. The observed relative risk reduction for flares associated with POF treatment was 54.9% (95% CI 0.21, 0.89) and the absolute risk reduction was 50.6% (95% CI 0.22, 0.80). Compared to placebo treatment, in the POF group, the mean prednisone dose was lower at 8 and 10 months (p = 0.007 and 0.01 respectively), and there was a trend towards less prednisone usage over the entire study period (p = 0.053), as determined by cumulative change analysis. CONCLUSIONS Although our exploratory post hoc analysis suggested that POF reduced flares and had steroid-sparing effects, given the study limitations, definitive conclusions cannot be drawn regarding the efficacy of POF in pulmonary sarcoidosis. In addition, gastrointestinal side-effects, at the doses used, would seem to limit the use of POF in treating pulmonary sarcoidosis. Overall, however, this trial may provide a basis for using more specific, better-tolerated, PDE inhibitors in future clinical trials.
Analysis of the Explanatory Variables of the Differences in Perceptions of Cyberbullying: A Role-Based-Model Approach

The controversies that exist regarding the delimitation of the cyberbullying construct demonstrate the need for further research focused on determining the criteria that shape the structure of the perceptions that adolescents have of this phenomenon and on seeking explanations of this behavior. The objectives of this study were to (a) construct possible explanatory models of the perception of cyberbullying from identifying and relating the criteria that form this construct and (b) analyze the influence of previous cyber victimization and cyber aggression experiences in the construction of explanatory models of the perception of cyberbullying. The sample consisted of 2,148 adolescents (49.1% girls; SD = 0.5) aged from 12 to 16 years (M = 13.9 years; SD = 1.2). The results have shown that previous cyber victimization and cyber aggression experiences lead to major differences in the explanatory models to interpret cyber-abusive behavior as cyberbullying episodes, or as social relationship mechanisms, or as a revenge reaction. We note that the aggressors’ explanatory model is based primarily on a strong reciprocal relationship between the imbalance of power and intentionality, that it functions as a link promoting indirect causal relationships of the anonymity and repetition factors with the cyberbullying construct. The victims’ perceptual structure is based on three criteria—imbalance of power, intentionality, and publicity—where the key factor in this structure is the intention to harm. These results allow to design more effective measures of prevention and intervention closely tailored to addressing directly the factors that are considered to be predictors of risk.
ATP‐driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling

The Mre11‐Rad50 complex is highly conserved, yet the mechanisms by which Rad50 ATP‐driven states regulate the sensing, processing and signaling of DNA double‐strand breaks are largely unknown. Here we design structure‐based mutations in Pyrococcus furiosus Rad50 to alter protein core plasticity and residues undergoing ATP‐driven movements within the catalytic domains. With this strategy we identify Rad50 separation‐of‐function mutants that either promote or destabilize the ATP‐bound state. Crystal structures, X‐ray scattering, biochemical assays, and functional analyses of mutant PfRad50 complexes show that the ATP‐induced ‘closed’ conformation promotes DNA end binding and end tethering, while hydrolysis‐induced opening is essential for DNA resection. Reducing the stability of the ATP‐bound state impairs DNA repair and Tel1 (ATM) checkpoint signaling in Schizosaccharomyces pombe, double‐strand break resection in Saccharomyces cerevisiae, and ATM activation by human Mre11‐Rad50‐Nbs1 in vitro, supporting the generality of the P. furiosus Rad50 structure‐based mutational analyses. These collective results suggest that ATP‐dependent Rad50 conformations switch the Mre11‐Rad50 complex between DNA tethering, ATM signaling, and 5′ strand resection, revealing molecular mechanisms regulating responses to DNA double‐strand breaks.
Cognitive-behavioral group treatments in childhood anxiety disorders: the role of parental involvement.

OBJECTIVES This study examined (1) the effect of a cognitive-behavioral group intervention on anxiety, depression, and coping strategies in school-age children (aged 7-12 years) with Axis I anxiety disorders; and (2) the effect of parental involvement on treatment outcomes. METHOD Parents and children (N = 62) were randomly assigned to one of three 12-week treatment conditions: parent and child intervention, child-only intervention, and parent-only intervention. Child anxiety, depression, and coping strategies were assessed before and after treatment. RESULTS All treatment groups reported fewer symptoms of anxiety and depression posttreatment and changes in their use of coping strategies. Children in the parent and child intervention used more active coping strategies posttreatment compared with children in the other 2 treatment conditions. Parents in this treatment condition reported a significantly greater improvement in their children's emotional well-being than parents in the other treatment conditions. CONCLUSIONS Cognitive-behavioral group interventions reduced symptoms of anxiety and depression in school-age children with anxiety disorders. Concurrent parental involvement enhanced the effect on coping strategies. Further investigation is needed to corroborate the effectiveness of such short-term interventions and the maintenance of treatment effects.
Antithrombotic properties of Ixolaris, a potent inhibitor of the extrinsic pathway of the coagulation cascade

Summary Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scapularis that presents extensive sequence homology t TFPI.It binds to FXa or FX as scaffolds and inhibits tissue factor/ FVIIa complex (extrinsic Xnase). Differently from TFPI, ixolaris does not bind to the active site cleft of FXa. Instead, comple formation is mediated by the FXa heparin-binding exosite,which may also results in decreased FXa activity into the prothrombi nase complex.In this report,we show that recombinant 125I-ixo laris interacts with rat and human FX in plasma and prolongs the prothrombin time (PT) and activated partial thromboplastin time (aPTT) in vitro.We have also investigated the effects of ixo laris in vivo, using a venous thrombosis model. Subcutaneous (s.c.) or intravenous (i.v.) administration of ixolaris in rats caused a dose-dependent reduction in thrombus formation, with complete inhibition attained at 20 µg/kg and 10 µg/kg, re spectively. Antithrombotic effects were observed 3 h after s.c. administration of ixolaris and lasted for 24 h thereafter. Ex vivo experiments showed that ixolaris (up to 100 µg/kg) did not affect the aPTT,while the PT was increased by ∼0.4-fold at the hig hest ixolaris concentration. Remarkably, effective antithrom botic doses of ixolaris (20 µg/kg) was not associated with bleed ing which was significant only at higher doses of the anticoagulant (40 µg/kg). Our experiments demonstrate that ixolaris is an effective and possibly safe antithrombotic agen in viv .
The Motivation of Employee Creativity:Employee Creative Self-efficacy

Creative self-efficacy,which is defined as the belief one has the ability to produce creative outcomes,plays an important role in the employee creative process.Creative self-efficacy explains as a person's belief that he or she can successfully perform in a particular setting,derived from Bandura's more general concept of self-efficacy.The main factors impact on employee creative self-efficacy is summarized:leadership support,the complexity of the work,the years of employee education,work experience and work self-efficacy.The relationship between creative self-efficacy and employee innovation is analysised,positive correlation between them is tested and verified by empirical studies.Finally,Some points about future trends on the research about creative self-efficacy are put forward,which is exploring more measurement tools,doing more empirical research on particular settings and trying to find more related factors.
Effect of Changes in Sleep Quantity and Quality on Depressive Symptoms Among Korean Children

This study aims to determine whether changes in sleep quantity and quality in childhood are associated with incidence of depressive symptoms. We used the three waves of the Korean Children & Youth Panel Survey (2011–2013). Statistical analysis using a generalized estimating equation model was performed. The 2,605 subjects analyzed included 1,453 students in 2012 and 1,152 students in 2013 without depressive symptoms in the prior year. We found that deteriorated or consistently poor sleep quality were important risk factors for depressive symptoms in children. We suggest that early detection and intervention of poor sleep quality in elementary school is required to reduce early onset depressive symptoms.
Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population

Background: Genetic polymorphisms that influence serotonin (5‐hydroxytryptamine, 5HT) neurotransmission are candidates for contributing to susceptibility to posttraumatic stress disorder (PTSD). The objective of our study was to determine if a variable length polymorphism for the promoter regions of the 5HT transporter (5HTTLPR), and/or a substitution polymorphism in the promoter region for the 5HT2A receptor, would be associated with PTSD in a trauma exposed population of adult African‐Americans. Methods: Using a case control design, 118 participants recruited from the primary care clinics and the campus of a historically black university who met inclusion criteria including trauma exposure provided blood samples for genomic DNA. PTSD criteria were determined by the Clinician Assessment of PTSD Scale (CAPS) and criteria for other psychiatric disorders by the Structured Clinical Interview for DSM‐IV (SCID). 5HTTLPR and 5HT2A‐1438A/G were genotyped using established methods. Associations of genotypes with lifetime PTSD, and models testing associations of allele “dose”, were analyzed. Results: Fifty‐five (47%) participants met lifetime criteria for PTSD and 26 (22%) met criteria for (mostly comorbid) major depression. The 5HT2A (lower expressing) G allele was significantly associated with PTSD. We did not find significant associations with 5HTTLPR. Conclusions: Our findings suggest a relationship between genetic variation in the 5HT2A promoter region and PTSD. Depression and Anxiety 26:993–997, 2009. Published 2009 Wiley‐Liss, Inc.