Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical evaluation of the PARP inhibitor BMN-673 for the treatment of ovarian clear cell cancer

Purpose To determine if models of ovarian clear cell carcinomas (OCCCs) harbouring defects in homologous recombination (HR) DNA repair of double strand breaks (DSBs) are sensitive to cisplatin and/or PARP inhibition. Experimental Design The HR status of 12 OCCC cell lines was determined using RAD51/γH2AX foci formation assays. Sensitivity to cisplatin and the PARP inhibitor BMN-673 was correlated with HR status. BRCA1, BRCA2, MRE11 and PTEN loss of expression was investigated as a potential determinant of BMN-673 sensitivity. A tissue microarray containing 50 consecutive primary OCCC was assessed for PTEN expression using immunohistochemistry. Results A subset of OCCC cells displayed reduced RAD51 foci formation in the presence of DNA DSBs, suggestive of HR defects. HR-defective OCCC cells, with the exception of KOC-7c, had higher sensitivity to cisplatin/ BMN-673 than HR-competent OCCC cell lines (Log10 SF50 –9.4 (SD +/− 0.29) vs –8.1 (SD +/− 0.35), mean difference 1.3, p < 0.01). Of the cell lines studied, two, TOV-21G and KOC-7c, showed loss of PTEN expression. In primary OCCCs, loss of PTEN expression was observed in 10% (5/49) of cases. Conclusions A subset of OCCC cells are sensitive to PARP inhibition in vitro, which can be predicted by HR defects as defined by γH2AX/RAD51 foci formation. These results provide a rationale for the testing of HR deficiency and PARP inhibitors as a targeted therapy in a subset of OCCCs.
Influence of a Microwave Irradiation on the Swelling and Permeation Properties of a Nafion Membrane

The effect of a microwave irradiation at 2450 MHz on the swelling and permeation properties of a Nafion membrane in water and methanol media has been studied. The influence of the irradiation power and the exposure time has been analyzed. The results found show that the irradiation hardly affects the membrane liquid uptake, but it affects the expansion properties of the membrane. The hydraulic permeability coefficient of the unmodified and the irradiated membranes has been experimentally determined. Higher hydraulic permeability has been obtained for the irradiated membranes in both water and methanol, but the degree of increment in permeability coefficient with microwave depends on kinds of permeation liquid. The results have been discussed considering the degradation effect occurring on the membrane hydrophobic matrix, which affects to the membrane elastic properties.
Prospective, Multicenter Study on Tinnitus Changes after Cochlear Implantation

Objective: To investigate the time course of tinnitus changes in patients receiving cochlear implantation (CI) in a prospective, multicenter setting and to determine related factors. Materials and Methods: A total of 79 adult patients who underwent CI were included in this study. We used the same questionnaires sequentially 5 times. The questionnaires included the Visual Analog Scale (VAS) for tinnitus severity, the Tinnitus Handicap Inventory (THI), Beck's Depression Index (BDI), and the Brief Encounter Psychosocial Instrument (BEPSI) for stress assessment. Results: Tinnitus was present in 59 (74.7%) of the 79 study subjects. After CI, tinnitus was eliminated in 10 patients (25%) and improved in 16 patients (40%) of the 40 patients who completed the final questionnaires, and most of the tinnitus reduction occurred in the early period of CI use. In an analysis of psychological functioning with CI, BDI was reduced significantly after CI. Multiple linear regression analysis revealed that preoperative auditory steady-state response (ASSR), THI, and final BDI score were significantly associated with the changes in tinnitus after CI. Conclusions: Most of the tinnitus reduction occurred within 1 month after CI use, and the changes were significantly associated with THI, ASSR, and BDI scores 6 months after CI. CI is a valuable therapeutic modality in tinnitus of a deafened ear.
Mammalian Gene PEG10 Expresses Two Reading Frames by High Efficiency –1 Frameshifting in Embryonic-associated Tissues*

Paternally expressed gene 10 (PEG10) is a mammalian gene that is essential for embryonic development in mice. The gene contains two overlapping open reading frames (ORF1 and ORF2) and is derived from a retroelement that acquired a cellular function. It is not known if both reading frames are required for PEG10 function. Synthesis of ORF2 would be possible only if programmed –1 frameshifting occurred during ORF1 translation. In this study the frameshifting activity of PEG10 was analyzed in vivo, and a potential role for ORF2 was investigated. Phylogenetic analysis demonstrated that PEG10 is highly conserved in therian mammals, with all species retaining the elements necessary for frameshifting as well as functional motifs in each ORF. The frameshift site of PEG10 was highly active in cultured cells and produced the ORF1-2 protein. In mice, endogenous ORF1 and an ORF1-2 frameshift protein were detected in the developing placenta and amniotic membrane from 9.5 days post-coitus through to term with a very high frameshift efficiency (>60%). Mutagenesis of the active site motif of a putative protease within ORF2 showed that this enzyme is active and participates in post-translational processing of PEG10 ORF1-2. Both PEG10 proteins were also detected in first trimester human placenta. By contrast, neither protein expression nor frameshifting was detected in adult mouse tissues. These studies imply that the ORF1-2 protein, synthesized utilizing the most efficient –1 frameshift mechanism yet documented in vivo, will have an essential function that is intrinsic to the importance of PEG10 in mammals.
Risk Profiles and Outcomes of Total Laparoscopic Hysterectomy Compared With Laparoscopically Assisted Vaginal Hysterectomy

OBJECTIVE: With the increasing rates of minimally invasive hysterectomy procedures serving as impetus, the aim of this study was to analyze the 30-day risk profiles associated with total laparoscopic hysterectomy and laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent a total laparoscopic hysterectomy or LAVH operation between 2006 and 2010. Patient demographics and 30-day complication rates were calculated. Multivariable regression analyses were used to study the effect of hysterectomy approach on outcomes. RESULTS: A total of 6,190 patients underwent laparoscopic hysterectomy, with 66.3% receiving LAVH and 33.7% receiving a total laparoscopic hysterectomy. The patient cohorts were well-matched. Although total laparoscopic hysterectomy procedures were significantly longer than LAVH operations (2.66 hours compared with 2.20 hours; P<.001), there was no difference in overall morbidity or reoperation rates between the LAVH and total laparoscopic hysterectomy populations (7.05% compared with 6.3% for overall morbidity; 1.3% compared with 1.7% for reoperation). Regression analyses revealed that surgical approach was not a significant predictor of overall postoperative morbidity or reoperation in minimally invasive hysterectomy patients. Additionally, obesity did not demonstrate a significant association with morbidity or reoperation rates; however, operative time was found to be a significant predictor of reoperation (odds ratio 1.23, 95% confidence interval 1.07–1.42). CONCLUSION: Laparoscopic hysterectomy is well-tolerated with total laparoscopic hysterectomy and LAVH, yielding comparable rates of postoperative morbidity and reoperation. On average, LAVH procedures were 28 minutes faster than total laparoscopic hysterectomy. Additionally, increasing body mass index was not associated with higher rates of morbidity. LEVEL OF EVIDENCE: II
Clear Cell Myoepithelial Carcinoma of Salivary Glands Showing EWSR1 Rearrangement: Molecular Analysis of 94 Salivary Gland Carcinomas With Prominent Clear Cell Component

This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary gland carcinomas with myoepithelial differentiation. A total of 94 salivary gland carcinomas with a prominent clear cell component included 51 cases of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign myoepithelioma were included as well. All the tumors in this spectrum were reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH) for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5 of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%) cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and CCMCexPAs shared similar histomorphology. They were arranged in nodules composed of compact nests of large polyhedral cells with abundant clear cytoplasm. Necrosis, areas of squamous metaplasia, and hyalinization were frequent features. Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%), and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in the 20% to 40% range. Clinical follow-up information was available in 21 cases (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to follow-up. Ten patients are alive with no evidence of recurrent or metastatic disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients are alive with recurrent and metastatic disease, and 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis appeared in 5 patients within 5 months to 4 years after diagnosis (mean 22 mo), distant metastases were noted in 7 patients with invasion of orbit (2 cases), and in 1 case each metastasis to the neck soft tissues, liver, lungs, mediastinum, and thoracic vertebra was noted. We describe for the first time EWSR1 gene rearrangement in a subset of myoepithelial carcinomas arising in minor and major salivary glands. The EWSR1-rearranged CCMC represents a distinctive aggressive variant composed predominantly of clear cells with frequent necrosis. Most EWSR1-rearranged CCMCs of salivary glands are characterized by poor clinical outcomes.
A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency

Stool consistency and frequency patterns are complex traits that are often altered in GI disease, and recent studies published in Gut highlight the importance of stool frequency in relation to gut microbiota composition and the efficacy of pharmacological and dietary treatments in IBS.1–3 Despite reported heritability in invertebrates4 and similar evidence from open-field defaecation models in rats,5 the genetics of stool frequency has not been explored in humans. We undertook a genome-wide association study (GWAS) in two well-characterised population-based cohorts with genotype and defaecation data available: LifeLines-Deep (LLD) from the Netherlands (N=1546; 58% females; mean age 44 years (range 18–86)) and PopCol (PC) from Sweden (N=284; 60% females; mean age 54 years (range 22–71)). 6 ,7 The average number of bowel movements per day (BM/d) was extracted from daily records kept by both populations and did not differ between cohorts (LLD=1.39±0.64SD; PC=1.42±0.74SD). Available CytoChip+Immunochip (LLD) and HumanOmniExpressExome (PC) Illumina single-nucleotide polymorphism (SNP) genotype data were imputed using IMPUTE2 (https://mathgen.stats.ox.ac.uk/impute/impute_v2.html) with the Genome of the Netherlands (http://www.nlgenome.nl/) as reference. SNPs were filtered on minor allele frequency >0.05 and Hardy–Weinberg equilibrium p>1E-04, samples were filtered on infoscore ≥0.8 and population outliers …
Effect of the bread-making process on zearalenone levels

The effects of the bread-making process including fermentation with Saccharomyces cerevisiae and lactic acid bacteria (Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus acidophilus and Lactobacillus fermentum) and baking at 200°C on zearalenone (ZEA) levels were investigated. Standard solutions of ZEA were added to flour and then loaves of bread were prepared. Sourdough and three types of yeast including active dry yeast, instant dry yeast and compressed yeast were used for the fermentation of dough. ZEA levels in flour, dough and bread were determined by HPLC with fluorescence detection after extraction and clean-up on an immunoaffinity column. The highest reduction in levels of ZEA was found in the first fermentation (first proof), while the lowest reduction was observed in the baking stage. In addition, the results showed that compressed yeast had the maximum reduction potential on ZEA levels even at the baking stage.
Bioinspired Ciliary Force Sensor for Robotic Platforms

The detection of small forces is of great interest in any robotic application that involves interaction with the environment (e.g., objects manipulation, physical human–robot interaction, minimally invasive surgery), since it allows the robot to detect the contacts early on and to act accordingly. In this letter, we present a sensor design inspired by the ciliary structure frequently found in nature, consisting of an array of permanently magnetized cylinders (cilia) patterned over a giant magnetoresistance sensor (GMR). When these cylinders are deformed in shape due to applied forces, the stray magnetic field variation will change the GMR sensor resistivity, thus enabling the electrical measurement of the applied force. In this letter, we present two 3 mm <inline-formula> <tex-math notation="LaTeX">$\times$</tex-math></inline-formula> 3 mm prototypes composed of an array of five cilia with 1 mm of height and 120 and 200 <inline-formula><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>m of diameter for each prototype. A minimum force of 333 <inline-formula><tex-math notation="LaTeX">$\mu$</tex-math> </inline-formula>N was measured. A simulation model for determining the magnetized cylinders average stray magnetic field is also presented.
Cross Talk between 2,4-Diacetylphloroglucinol-Producing Biocontrol Pseudomonads on Wheat Roots

ABSTRACT The performance of Pseudomonas biocontrol agents may be improved by applying mixtures of strains which are complementary in their capacity to suppress plant diseases. Here, we have chosen the combination of Pseudomonas fluorescens CHA0 with another well-characterized biocontrol agent, P. fluorescens Q2-87, as a model to study how these strains affect each other's expression of a biocontrol trait. In both strains, production of the antimicrobial compound 2,4-diacetylphloroglucinol (DAPG) is a crucial factor contributing to the suppression of root diseases. DAPG acts as a signaling compound inducing the expression of its own biosynthetic genes. Experimental setups were developed to investigate whether, when combining strains CHA0 and Q2-87, DAPG excreted by one strain may influence expression of DAPG-biosynthetic genes in the other strain in vitro and on the roots of wheat. DAPG production was monitored by observing the expression of lacZ fused to the biosynthetic gene phlA of the respective strain. Dual-culture assays in which the two strains were grown in liquid medium physically separated by a membrane revealed that Q2-87 but not its DAPG-negative mutant Q2-87::Tn5-1 strongly induced phlA expression in a ΔphlA mutant of strain CHA0. In the same way, phlA expression in a Q2-87 background was induced by DAPG produced by CHA0. When coinoculated onto the roots of wheat seedlings grown under gnotobiotic conditions, strains Q2-87 and CHA0, but not their respective DAPG-negative mutants, were able to enhance phlA expression in each other. In summary, we have established that two nonrelated pseudomonads may stimulate each other in the expression of an antimicrobial compound important for biocontrol. This interpopulation communication occurs in the rhizosphere, i.e., at the site of pathogen inhibition, and is mediated by the antimicrobial compound itself acting as a signal exchanged between the two pseudomonads.
Audio-Visual Integration in a Redundant Target Paradigm: A Comparison between Rhesus Macaque and Man

The mechanisms underlying multi-sensory interactions are still poorly understood despite considerable progress made since the first neurophysiological recordings of multi-sensory neurons. While the majority of single-cell neurophysiology has been performed in anesthetized or passive-awake laboratory animals, the vast majority of behavioral data stems from studies with human subjects. Interpretation of neurophysiological data implicitly assumes that laboratory animals exhibit perceptual phenomena comparable or identical to those observed in human subjects. To explicitly test this underlying assumption, we here characterized how two rhesus macaques and four humans detect changes in intensity of auditory, visual, and audio-visual stimuli. These intensity changes consisted of a gradual envelope modulation for the sound, and a luminance step for the LED. Subjects had to detect any perceived intensity change as fast as possible. By comparing the monkeys' results with those obtained from the human subjects we found that (1) unimodal reaction times differed across modality, acoustic modulation frequency, and species, (2) the largest facilitation of reaction times with the audio-visual stimuli was observed when stimulus onset asynchronies were such that the unimodal reactions would occur at the same time (response, rather than physical synchrony), and (3) the largest audio-visual reaction-time facilitation was observed when unimodal auditory stimuli were difficult to detect, i.e., at slow unimodal reaction times. We conclude that despite marked unimodal heterogeneity, similar multisensory rules applied to both species. Single-cell neurophysiology in the rhesus macaque may therefore yield valuable insights into the mechanisms governing audio-visual integration that may be informative of the processes taking place in the human brain.
Myosin isoforms in anuran skeletal muscle: Their influence on contractile properties and in vivo muscle function

Functional studies on isolated single anuran skeletal muscle cells represent classic experiments from which much of our understanding of muscle contraction mechanisms have been derived. Because of their superb mechanical stability when isolated, single anuran fibers provide a uniquely powerful model system that can be exploited to understand the relationship between myosin heavy chain (MHC) and myosin light chain (MLC) composition and muscle fiber function. In this review, we summarize historic and recent studies of MHC and MLC expression patterns in the fiber types of anuran species. We extend the traditional classification scheme, using data from recent reports in which frog MHCs have been cloned, to reveal the molecular basis of frog muscle fiber types. The influence of MHC and MLC isoforms on contractile kinetics of single intact fibers is reviewed. In addition, we discuss more subtle questions such as variability of myosin coexpression along a single cell, and its potential influence on contractile function. The frog jump is used as a model system to elucidate principles of muscular system design, including the role of MHC isoforms on in vivo muscle function. Sequence information is used from cloned frog MHCs to understand the role of specific regions of the myosin motor domain in regulating contractile function and the evolutionary origins of fast and slow amphibian MHCs. Finally, we offer promising future possibilities that combine molecular methods (such as recombinant gene transfer) with single cell contractile measurements to address questions regarding myosin structure/function and gene regulation. Microsc. Res. Tech. 50:443–457, 2000. © 2000 Wiley‐Liss, Inc.
A high eating frequency is associated with an overall healthy lifestyle in middle-aged men and women and reduced likelihood of general and central obesity in men

The role of eating frequency in obesity development is debated. Therefore, we investigated the association between eating frequency, BMI and waist circumference (WC), as well as how eating frequency is related to diet composition and lifestyle factors. A subsample (aged 47–68 years) of men (n 1355) and women (n 1654) from the Malmö Diet and Cancer cohort was used for the present cross-sectional study. The daily eating frequency was calculated based on the number of self-reported eating occasions during an ordinary day. Regression analysis and ANOVA examined the associations between eating frequency, BMI and WC, while adjusting for potential confounders. The energy percentage (E%) from carbohydrates as well as relative fibre intake (g/MJ) increased with higher eating frequency; while E% from fat, protein and alcohol decreased. A low daily eating frequency was associated with smoking, higher alcohol consumption, and lower leisure-time physical activity. Eating three or fewer meals per d was also associated with increased likelihood of general and central obesity in men when adjusting for total energy intake, lifestyle and dietary factors. However, results did not reach statistical significance among women. The present study suggests that a high daily eating frequency is associated with a healthy lifestyle and dietary pattern in both men and women, and a reduced likelihood of general and central obesity in men. There is a need for prospective studies investigating the association between eating frequency, diet and body composition.
Forgiveness, Depression, and Suicidal Behavior in Adolescents: Gender Differences in this Relationship

ABSTRACT With the development of positive psychology, protective factors have received increased attention as buffers against suicidal ideation and attempts and against the risk factors for suicide (e.g., depressive symptoms). Empirical evidence suggests that one of the protective factors associated with depression and suicide is forgiveness. Although previous studies have demonstrated a negative association between forgiveness and risk of suicide, studies on gender differences in adolescents are still scarce. Thus, the authors assessed the moderating role of gender in a sample of adolescents. The participants were 572 adolescents (50.9% boys; M age = 15.49 years, SD = 1.09 years) from secondary school centers. The results revealed that forgiveness moderated the relationship between depression and suicidal ideation for boys but not for girls. Specifically, for boys the relationship between depression and suicidal thoughts and behaviors weakened as levels of forgiveness increased. These findings suggest therapeutic applications to reduce the likelihood of suicide in the group of adolescent boys with higher scores on depression and lower levels of forgiveness. The study results are discussed in terms of the need to use gender perspectives in positive psychology intervention programs.