Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of MED12 Mutation in Multiple Uterine Leiomyomas in South Korean patients

Uterine leiomyomas are one of the most common benign gynecologic tumors, but the exact causes are not completely understood. In 2011, through DNA sequencing, MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several recent studies confirmed the high frequency of MED12 mutation in uterine leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of patients with multiple leiomyomas in a patient. The purpose of this study was to investigate the frequency of MED12 mutations in uterine leiomyomas of South Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas in the same patients. Uterine leiomyoma tissues were obtained from symptomatic women who underwent hysterectomy or myomectomy for medically indicated reasons. We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to 12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14 patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three of them had the same mutations. Five of them, each leiomyoma had a different mutation. Two of them did not have mutation. Four of them had both mutation-positive and mutation-negative leiomyomas. In conclusion, we confirmed the high frequency of the MED12 mutation in uterine leiomyomas of South Korean patients. We also identified various MED12 mutation status in patients with multiple leiomyomas. This suggests that in a given patient, different tumors may have arisen from different cell origins and therefore it is supposed that occurrence of multiple leiomyoma in a single patient may not be caused by intrauterine metastasis or dissemination.
Risk assessment and lipid modification for primary and secondary prevention of cardiovascular disease: summary of NICE guidance

Cardiovascular disease remains a leading cause of morbidity and mortality in the United Kingdom. Randomised controlled trials have shown benefit from modifying risk factors in people at risk of developing cardiovascular disease and in those who have evidence of established disease. Currently patients are often assessed opportunistically and treated on the basis of individual clinical or laboratory results rather than on their overall level of risk of developing cardiovascular disease. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the effective identification and assessment of people at risk of cardiovascular disease, and on the modification of lipids in primary and secondary prevention. The detailed consideration of the evidence is available in the full guideline (www.nice.org.uk/ CG67). 1 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the guideline development group’s opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Identifying those at risk of cardiovascular disease for primary prevention
Role of the Pseudomonas aeruginosa PlcH Tat Signal Peptide in Protein Secretion, Transcription, and Cross-Species Tat Secretion System Compatibility

ABSTRACT The secretion of PlcH and its homolog PlcN of Pseudomonas aeruginosa through the inner membrane depends upon a functional twin arginine translocase (Tat) system and a Tat signal sequence. Conserved twin arginine (Arg) residues within the Tat signal sequence consensus motif (S/TRRxFLK) are considered essential for the secretion of Tat substrates, but some exceptions (e.g., Lys and Arg) to the twin Arg residues in this motif have been noted. The roles of all three Arg residues within the PlcH RRRTFLK consensus motif were examined. Data are presented which indicate that Arg-9 and Arg-10 are essential for PlcH secretion across the inner membrane, but the mutation of Arg-8 (e.g., to Ala or Ser) had no observable effect on the localization of PlcH. In the signal sequence of PlcH and in all of its homologs in other bacteria, there are basic amino acid residues (Arg, Lys, and Gln) immediately adjacent to the signal peptidase cleavage site (Ala-X-Ala) that are not seen in Sec-dependent signal sequences. The mutation of these basic residues to Ala caused slightly decreased levels of extracellular PlcH, but normal localization was still observed. Deletion of the entire Tat signal sequence of PlcH not only resulted in the absence of detectable extracellular PlcH activity and protein but also caused a substantial decrease in the detectable level of plcH mRNA. Finally, data are presented which indicate that P. aeruginosa PlcH exhibits cross-species compatibility with the Escherichia coli Tat secretion machinery, but only when the E. coli Tat machinery is expressed in a P. aeruginosa host.
Thermodynamic Sensing Mechanisms of AlGaN-Based Metal/Reactive Insulator/Semiconductor-Type Hydrogen Sensors

Thermodynamic sensing mechanisms of Pt/reactive insulator/AlGaN hydrogen sensors were studied. The reactive insulator layer of mixed and was grown directly from the AlGaN layer using a photoelectrochemical oxidation method. The current of the hydrogen sensors exhibited considerable response under forward bias in a hydrogen ambient at the temperature range between 350 K and 550 K. Based on the steady-state analysis, the adsorption enthalpy of for hydrogen adsorbed at the interface and in the reactive insulator layer was obtained. Because the kinetic reaction was an exothermic action, the hydrogen response decreased with an increase of operating temperatures. From the thermodynamic kinetic analysis of transient responses, the activation energy was 3.57 kJ/mol. The Pt/reactive insulator/AlGaN hydrogen sensors exhibited high performance at various temperatures.
Echocardiographic parameters in adolescents with sleep‐related breathing disorders

Few data are known about the effects of sleep‐related breathing disorders (SRBD) on the cardiovascular system in adolescents. Forty healthy adolescents (mean age, 13.7 ± 1.6 years) answered a questionnaire regarding symptoms of sleep‐related breathing disorders (SRBD) and underwent a cardiorespiratory polygraphy and echocardiography. Echocardiographic data in snorers with polygraphic abnormalities suggestive of SRBD (positive group, n = 29) were compared with the results in nonsnorers without polygraphic abnormalities (n = 11) who were included in the control group. Ventricular dimensions and indices of left ventricular systolic function were within normal limits and were not significantly different between the two groups. Indices of left ventricular diastolic function were also within normal limits, but isovolumetric relaxation time (IVRT) was significantly longer among the positive group (72.5 ± 8.4 msec) than among the controls (65.1 ± 7.9 msec) (P = 0.018). Multiple regression analysis showed that posterior wall thickness was predicted by a model that included cardiac events related with respiratory events and/or desaturations, and respiratory disturbance index (RDI) in supine position. Deceleration of early diastolic flow was predicted by RDI, percentage of total recording time with SaO2 < 90% (CT90), and age; the variability of isovolumetric relaxation time was predicted by a model that included RDI in supine position. We found a significant relationship between polygraphic parameters suggestive of SRBD and echocardiographic measurements of ventricular dimensions and diastolic function. Also, echocardiographic parameters suggestive of some degree of left ventricular diastolic dysfunction were found in snoring adolescents with polygraphic abnormalities. Pediatr Pulmonol. 2003; 36:27–33. © 2003 Wiley‐Liss, Inc.
The epidemiology of gonorrhoea, chlamydial infection and syphilis in four African cities

Objectives: To compare the epidemiology of gonorrhoea, chlamydial infection and syphilis in four cities in sub-Saharan Africa; two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon). Design: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa. Methods: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) Trichomonas vaginalis infection. Risk factor analyses were carried out for chlamydial infection and syphilis seroreactivity. Results: The prevalence of gonorrhoea ranged between 0% in men in Kisumu and 2.7% in women in Yaoundé. Men and women in Yaoundé had the highest prevalence of chlamydial infection (5.9 and 9.4%, respectively). In the other cities, the prevalence of chlamydial infection ranged between 1.3% in women in Cotonou and 4.5% in women in Kisumu. In Ndola, the prevalence of syphilis seroreactivity was over 10% in both men and women; it was around 6% in Yaoundé, 3-4% in Kisumu, and 1-2% in Cotonou. Chlamydial infection was associated with rate of partner change for both men and women, and with young age for women. At the population level, the prevalence of chlamydial infection correlated well with reported rates of partner change. Positive syphilis serology was associated with rate of partner change and with HSV-2 infection. The latter association could be due to biological interaction between syphilis and HSV-2 or to residual confounding by sexual behaviour. At the population level, there was no correlation between prevalence of syphilis seroreactivity and reported rates of partner change Conclusion: Differences in prevalence of chlamydial infection could be explained by differences in reported sexual behaviour, but the variations in prevalence of syphilis seroreactivity remained unexplained. More research is needed to better understand the epidemiology of sexually transmitted infections in Africa.
Laterality patterns in infants with external birth defects.

The lateral distribution of external birth defects has not been reported in a comprehensive way, and patterns in this distribution have not been examined. This study presents the lateral distribution of 6,390 unilateral defects from among 102 defect categories in data collected by the Metropolitan Atlanta Congenital Defects Program. Among all defects, 49% (95% CI 48-51%) were right-sided. Among males and females, 51% (95% CI 50-53%) and 47% (95% CI 46-49%) of the defects, respectively, were right-sided. Of the 102 defect types, 57 had an excess of defects on the right side of the body; 39 had an excess of defects on the left side; and 6 were equally distributed. The excess on the right side was statistically significant for inguinal hernia, incarcerated inguinal hernia, microtia, preauricular sinus, talipes calcaneovalgus, and lambdoidal craniosynostosis. For the left side, the excess was statistically significant for preauricular tags, cleft lip, fused lip and cleft gum, cleft lip with cleft palate, congenital hip dysplasia, unstable hip, absent forearm or hand, anomaly of the knee, and skin tags. The percentage of right-sided defects among case subjects with unilateral defects was correlated with the percentage of males among all case subjects (r = 0.24, P < 0.05). Among male case subjects with unilateral defects, the correlation coefficient was 0.31 (P < 0. 01), and among females with unilateral defects, it was 0.11 (P > 0. 10). Differences in the lateral distribution of specific birth defects may be due to subtle differences in morphogenesis on the left and right sides of the embryo brought about by establishment of left-right asymmetry prior to organogenesis. The fact that more defect categories were right-sided than left-sided may be related to the observation that mitochondrial maturation in rat embryos is delayed on the right side. The right side, therefore, may be more susceptible than the left to defects caused by prenatal hypoxia. The significant correlation between the percentage right-sided and percentage male may then also be related to the observation that male sex hormones lower the mitochondrial respiration rate in rats and increase rat sensitivity to chemical hypoxia. Investigators should consider reporting the laterality of specific defects in both laboratory and epidemiological studies of birth defects. Right- and left-sided defects should perhaps be considered separately in etiologic studies of birth defects. Teratology 60:265-271, 1999. Published 1999 Wiley-Liss, Inc.
Theory of dielectric breakdown in metal-loaded dielectrics.

We have examined a very simple model of dielectric breakdown in random mixtures of metal and dielectric.1,2,3 We expect this analysis to be relevant for an class of materials which are composed of a random mixture of metallic particles embedded in a dielectric matrix. An example is solid fuel rocket propellant4 which is a mixture of microscopic aluminum particles (the fuel) in a dielectric matrix composed of oxidizer and rubber binder. The model we analyze is a percolation model in which the bonds of a d-dimensional lattice with lattice spacing a are occupied by conductors with probability p and by capacitors with probability 1-p. The probability p is chosen to be less than the percolation threshold pc so that no conducting path traverses the entire system. The breakdown process is modeled by assuming that the capacitors can withstand a maximum voltage drop of 1 volt. The entire lattice has a size of L lattice spacings. A macroscopic voltage is applied across the lattice. This voltage is raised until the voltage drop across one of the capacitors exceeds 1 volt. This macroscopic voltage is called V1 the initial breakdown voltage. The capacitor which fails is replaced by a conducting element. The process of failing one of the capacitors is repeated until a conducting path is formed across the sample. The maximum value of the applied voltage during this procedure is called the complete breakdown voltage and is denoted Vb.
DIRECT EVIDENCE FOR GRAVITATIONAL INSTABILITY AND MOONLET FORMATION IN SATURN’s RINGS

New images from the Cassini spacecraft reveal optically thick clumps, capable of casting shadows, and associated structures in regions of Saturn's F ring that have recently experienced close passage by the adjacent moon Prometheus. Using these images and modeling, we show that Prometheus’ perturbations create regions of enhanced density and low relative velocity that are susceptible to gravitational instability and the formation of distended, yet long-lived, gravitationally coherent clumps. Subsequent collisional damping of these low-density clumps may facilitate their collapse into ∼10–20 km contiguous moonlets. The observed behavior of the F ring is analogous to the case of a marginally stable gas disk being driven to instability and collapse via perturbations from an embedded gas giant planet.
Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation

BACKGROUND Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin. OBJECTIVE To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF. DESIGN Markov decision model. DATA SOURCES The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom. TARGET POPULATION Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS₂ score ≥1 or equivalent) and no contraindications to anticoagulation. TIME HORIZON Lifetime. PERSPECTIVE Societal. INTERVENTION Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose). OUTCOME MEASURES Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran. RESULTS OF SENSITIVITY ANALYSIS The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage. LIMITATION Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up. CONCLUSION In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS₂ score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States. PRIMARY FUNDING SOURCE American Heart Association and Veterans Affairs Health Services Research & Development Service.
Increased Proliferation and Gliogenesis of Cultured Rat Neural Progenitor Cells by Lipopolysaccharide-Stimulated Astrocytes

Neural progenitor cells (NPC) are self-renewing multipotent cells that generate neurons and glial cells in the brain. NPCs generate neurons and glia not only during development but also after neural injury. Recent studies have shown that endogenous NPCs are activated after brain injury and migrate toward damaged areas where astrocyte activation occurs. Considering the massive proliferation of astrocytes as well as the production of several kinds of cytoactive molecules after brain injury, such as NO, growth factors and cytokines, it is tempting to think that cytoactive molecules released by activated glial cells regulate neural progenitor differentiation and proliferation through inflammatory mediators. To test this hypothesis, we stimulated rat primary astrocytes with lipopolysaccharide (LPS) to induce the activation of astrocytes. After addition of the conditioned media from LPS-stimulated astrocytes to NPC culture, proliferation was examined by MTT assay and bromodeoxyuridine (BrdU) incorporation. The differentiation of NPC into neurons and astrocytes was examined by Western blot, ELISA and immunocytochemical staining with cell-type-specific mark- ers. Conditioned media from LPS-stimulated astrocytes increased NPC proliferation as well as gliogenesis as compared with control conditioned media from astrocytes without LPS stimulation. In contrast, neurogenesis was decreased by LPS-conditioned media. To investigate the molecular mechanism mediating glial differentiation and proliferation of NPC by reactive astrocytes, we added inhibitors of the Erk and JNK pathways during LPS stimulation. These inhibitors – except for a p38 inhibitor – decreased NPC proliferation and glial differentiation. These results suggest that LPS stimulated astrocytes generate factors regulating NPC proliferation and gliogenesis via the Erk and JNK pathways.
IgE responses in human filariasis. I. Quantitation of filaria-specific IgE.

We have developed a noncompetitive solid phase radioimmunoassay to quantitate human IgE antibodies against soluble adult antigens of Brugia malayi (B.m.), a filarial parasite, in sera of patients with various forms of clinical filariasis in Madras, India. A single reference serum was shown to contain 23 micrograms/ml of B.m. -specific IgE by depletion analysis and was used as a standard serum throughout the study. The levels of specific IgE ranged in the patients sera from 2 to 23,000 ng/ml. When these individuals were divided into clinical groups, the individuals with tropical pulmonary eosinophilia had the highest levels (mean = 8630 ng/ml) and were significantly higher than all the other groups (p less than 0.001). The lowest levels were seen in patients with circulating microfilariae (mean = 30.5 ng/ml). Patients exhibiting lymphatic obstruction (i.e., chronic pathology group) had levels slightly higher than microfilaremics (mean = 68 ng/ml) but were not significantly different (p less than 0.1). Surprisingly, individuals living in endemic areas but who had no clinical signs of filariasis also showed appreciable levels of B.m. -specific IgE (mean = 55 ng/ml). The B.m. -specific IgE represented 0.1 to 48% of the total IgE. High percentages of specific IgE may be responsible for evoking allergic symptomatology in patients with tropical pulmonary eosinophilia.
Estimate of true incomplete exchanges using fluorescence in situ hybridization with telomere probes.

PURPOSE To study the frequency of true incomplete exchanges in radiation-induced chromosome aberrations. MATERIALS AND METHODS Human lymphocytes were exposed to 2 Gy and 5 Gy of gamma-rays. Chromosome aberrations were studied using the fluorescence in situ hybridization (FISH) technique with whole chromosome-specific probes, together with human telomere probes. Chromosomes 2 and 4 were chosen in the present study. RESULTS The percentage of incomplete exchanges was 27% when telomere signals were not considered. After excluding false incomplete exchanges identified by the telomere signals, the percentage of incomplete exchanges decreased to 11%. Since telomere signals appear on about 82% of the telomeres, the percentage of true incomplete exchanges should be even lower and was estimated to be 3%. This percentage was similar for chromosomes 2 and 4 and for doses of both 2 Gy and 5 Gy. CONCLUSIONS The percentage of true incomplete exchanges is significantly lower in gamma-irradiated human lymphocytes than the frequencies reported in the literature.