Miracle-dz/UniFAR-FTUs huggingface dataset:
Fusion of the genes BRD8 and PHF1 in endometrial stromal sarcoma

We present a new endometrial stromal sarcoma (ESS)‐associated genomic rearrangement involving chromosome arms 5p and 6p and leading to the formation of a BRD8‐PHF1 fusion gene. The PHF1 (PHD finger protein 1) gene, from 6p21, is known to be rearranged in ESS in a promiscuous way inasmuch as it has been shown to recombine with JAZF1, EPC1, MEAF6, and now also with BRD8, in tumors of this type. In all rearrangements of PHF1, including the present one, a recurrent theme is that the entire coding part of PHF1 constitutes the 3′ end of the fusion. BRD8 (bromodomain containing 8) encodes a protein which is involved in regulation of protein acetylation and/or histone acetyl transferase activity. All the genetic fusions identified so far in ESS appear to recombine genes involved in transcriptional regulation, that is, polycomb group complex‐mediated and aberrant methylation/acetylation genes. This adds to the likelihood that the new BRD8‐PHF1 shares the same pathogenetic mechanism as the other ESS‐specific rearrangements.
Development of glucose measurement system based on pulsed laser-induced ultrasonic method

In this study, a kind of glucose measurement system based on pulsed-induced ultrasonic technique was established. In this system, the lateral detection mode was used, the Nd: YAG pumped optical parametric oscillator (OPO) pulsed laser was used as the excitation source, the high sensitivity ultrasonic transducer was used as the signal detector to capture the photoacoustic signals of the glucose. In the experiments, the real-time photoacoustic signals of glucose aqueous solutions with different concentrations were captured by ultrasonic transducer and digital oscilloscope. Moreover, the photoacoustic peak-to-peak values were gotten in the wavelength range from 1300nm to 2300nm. The characteristic absorption wavelengths of glucose were determined via the difference spectral method and second derivative method. In addition, the prediction models of predicting glucose concentrations were established via the multivariable linear regression algorithm and the optimal prediction model of corresponding optimal wavelengths. Results showed that the performance of the glucose system based on the pulsed-induced ultrasonic detection method was feasible. Therefore, the measurement scheme and prediction model have some potential value in the fields of non-invasive monitoring the concentration of the glucose gradient, especially in the food safety and biomedical fields.
Glottal Aerodynamic Measures in Women With Phonotraumatic and Nonphonotraumatic Vocal Hyperfunction.

Purpose The purpose of this study was to determine the validity of preliminary reports showing that glottal aerodynamic measures can identify pathophysiological phonatory mechanisms for phonotraumatic and nonphonotraumatic vocal hyperfunction, which are each distinctly different from normal vocal function. Method Glottal aerodynamic measures (estimates of subglottal air pressure, peak-to-peak airflow, maximum flow declination rate, and open quotient) were obtained noninvasively using a pneumotachograph mask with an intraoral pressure catheter in 16 women with organic vocal fold lesions, 16 women with muscle tension dysphonia, and 2 associated matched control groups with normal voices. Subjects produced /pae/ syllable strings from which glottal airflow was estimated using inverse filtering during /ae/ vowels, and subglottal pressure was estimated during /p/ closures. All measures were normalized for sound pressure level (SPL) and statistically tested for differences between patient and control groups. Results All SPL-normalized measures were significantly lower in the phonotraumatic group as compared with measures in its control group. For the nonphonotraumatic group, only SPL-normalized subglottal pressure and open quotient were significantly lower than measures in its control group. Conclusions Results of this study confirm previous hypotheses and preliminary results indicating that SPL-normalized estimates of glottal aerodynamic measures can be used to describe the different pathophysiological phonatory mechanisms associated with phonotraumatic and nonphonotraumatic vocal hyperfunction.
Automatic Summarization for Terminology Recommendation: The Case of the NCBO Ontology Recommender

The National Center for Biomedical Ontology (NCBO) ontology recommender helps users choose a biomedical terminology by analyzing a submitted document. Submitting a single document might not be representative and result in poor recommendations, while submitting a large sample might be expensive, sometimes unfeasible. In this paper, we investigate the effectiveness of two well-researched automatic summarization techniques as an alternative: topic modeling using Latent Dirichlet Allocation and keyword extraction using TextRank. In our case study, both techniques proved to be extremely valuable, dramatically boosting performance without significantly affecting terminology recommendations (r = 0.83–0.98).
Sintering of a-Al2O3-seeded nanocrystalline g-Al2O3 powders

This paper demonstrates that seeding nanocrystalline transition alumina powders is a viable option for producing high quality, alumina-based ceramics. By using a-Al2O3 concentrations of 51.25 wt. % a-Al2O3 seed particles (equivalent to 5 � 10 14 seeds/cm 3 of g-Al2O3) the sintering temperature is reduced from 1600 � C for unseeded g-Al2O3 to 1300–1400 � C in dry pressed powders. The scale of the sintered microstructure is related to Nv 1/3 and thus a 100-nm grain size is obtained. It is apparent that seeding is necessary for producing dense, alumina-based ceramics from nanocrystalline transition alumina powders. # 2002 Elsevier Science Ltd. All rights reserved.
The contribution of alternative splicing to genetic risk for psychiatric disorders

A genetic contribution to psychiatric disorders has clearly been established and genome‐wide association studies now provide the location of risk genes and genetic variants associated with risk. However, the mechanism by which these genes and variants contribute to psychiatric disorders is mostly undetermined. This is in part because non‐synonymous protein coding changes cannot explain the majority of variants associated with complex genetic traits. Based on this, it is predicted that these variants are causing gene expression changes, including changes to alternative splicing. Genetic changes influencing alternative splicing have been identified as risk factors in Mendelian disorders; however, currently there is a paucity of research on the role of alternative splicing in complex traits. This stems partly from the difficulty of predicting the role of genetic variation in splicing. Alterations to canonical splice site sequences, nucleotides adjacent to splice junctions, and exonic and intronic splicing regulatory sequences can influence splice site choice. Recent studies have identified global changes in alternatively spliced transcripts in brain tissues, some of which correlate with altered levels of splicing trans factors. Disease‐associated variants have also been found to affect cis‐acting splicing regulatory sequences and alter the ratio of alternatively spliced transcripts. These findings are reviewed here, as well as the current datasets and resources available to study alternative splicing in psychiatric disorders. Identifying and understanding risk variants that cause alternative splicing is critical to understanding the mechanisms of risk as well as to pave the way for new therapeutic options.
The effects of soybean isoflavones and 17β-estradiol in uterus and mammary glands of diabetic rat models

Abstract The objective of this study was to evaluate the action of soy isoflavones and 17 beta estradiol on the extracellular matrix in the uterus and mammary gland of diabetic rats. Sixty adult female rats underwent ovariectomy, then randomized into seven groups of ten animals each: Non-diabetic: GI Sham control animals ovariectomized; and GII control ovariectomized that received propylene glycol vehicle. Diabetic: GIII Sham control diabetic animals ovariectomized; GIV ovariectomized diabetic animals receiving propylene glycol vehicle; GV diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI ovariectomized diabetic rats treated with estrogen (17b-estradiol, 10 mg/kg, subcutaneously); GVII diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage), and with estrogen (17b-estradiol, 10 mg/kg combination therapy). Treatments occurred during 30 consecutive days. After animals euthanasia, a portion of the uterus was immersed in liquid nitrogen for molecular biology analysis, the other portion of uterus and mammary glands were removed and processed for paraffin embedding. Soy isoflavones (GV) and 17b estradiol improved the production of compounds of extracellular matrix, such as small leucine-rich proteoglycans (SLRPs). The combination of both therapies had an additive effect in SLRPs expression. Soy isoflavones contribute to the uterine integrity of SLRPs of diabetic rats.
Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration

See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical background for studies that seek the mechanisms by which cognitive and motor dysfunctions arise from cerebellar degeneration. Beyond replicating these findings, future research should employ experimental tasks to probe the integrity of specific functions in cerebellar disease, and new imaging methods to quantitatively map atrophy across the cerebellum.
Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

Significance The gradual aging of the immune system is partly marked by shortened telomeres, the DNA–protein caps at the ends of chromosomes that protect genes from degradation. This study undertakes a lifespan approach to stress and leukocyte telomere length in a nationally representative sample of US residents. By using data from 16 y of the Health and Retirement Study, childhood and adulthood life stressors were examined for their individual and combined associations with increased odds of having short telomeres. Accumulated adverse experiences in childhood significantly predicted an increased likelihood of having short telomeres later in life, suggesting a potential pathway through which childhood experiences have been previously shown to predict adulthood morbidity and mortality. Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.
In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP

In vivo imaging shows that the great majority of somatosensory neurons are modality-specific. Mechanistic insights into pain pathways are essential for a rational approach to treating this vast and increasing clinical problem. Sensory neurons that respond to tissue damage (nociceptors) may evoke pain sensations and are typically classified on the basis of action potential velocity. Electrophysiological studies have suggested that most of the C-fiber nociceptors are polymodal, responding to a variety of insults. In contrast, gene deletion studies in the sensory neurons of transgenic mice have frequently resulted in modality-specific deficits. We have used an in vivo imaging approach using the genetically encoded fluorescent calcium indicator GCaMP to study the activity of dorsal root ganglion sensory neurons in live animals challenged with painful stimuli. Using this approach, we can visualize spatially distinct neuronal responses and find that >85% of responsive dorsal root ganglion neurons are modality-specific, responding to either noxious mechanical, cold, or heat stimuli. These observations are mirrored in behavioral studies of transgenic mice. For example, deleting sodium channel Nav1.8 silences mechanical- but not heat-sensing sensory neurons, consistent with behavioral deficits. In contrast, primary cultures of axotomized sensory neurons show high levels of polymodality. After intraplantar treatment with prostaglandin E2, neurons in vivo respond more intensely to noxious thermal and mechanical stimuli, and additional neurons (silent nociceptors) are unmasked. Together, these studies define polymodality as an infrequent feature of nociceptive neurons in normal animals.
Materials under Shock Loading: from Biot's Theory to Nano-Poromechanics

Porous materials are known to be effective in mitigating the impact of shock/blast waves. Nano-structured materials appear to have an even greater potential for such mitigation because of their high surface-to-volume ratio, a property which attenuates shock wave propagation substantially. Molecular dynamics was used to explore the effects of this remarkable characteristic on the behavior of traveling shocks impacting on solid materials with and without a porous structure attached. The materials involved were represented by realistic interaction potentials. Cases with various values of porosity have been investigated and the results indicate that the presence of a nano-porous material layer in front of a target wall reduces the energy deposited inside the solid by about 30 percent, while at the same time considerably decreasing its loading rate.
The control of translational accuracy is a determinant of healthy ageing in yeast

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing.
Body fatness throughout the life course and the incidence of premenopausal breast cancer.

BACKGROUND The role of body fatness in the aetiology of breast cancer is complex. We evaluated the independent and synergistic effects of body fatness, at different stages throughout a woman's life course, on premenopausal breast cancer risk. METHODS Premenopausal participants of the Nurses' Health Study II (NHSII) were followed from 1991 up to 2009. Body fatness factors including birthweight, somatotype (a 9-level pictogram with level 1 being the leanest) at ages 5 and 10 years and body mass index (BMI) at age 18 were collected at baseline. Current BMI was updated biennially. Multivariate Cox regression models were used to evaluate the association between each body fatness factor as well as cross-classification of all factors and the incidence of breast cancer. RESULTS Based on 1574 incident premenopausal breast cancer cases and 1 133 893 person-years of follow-up, a lower incidence was associated with lower birthweight: hazard ratio (HR) [95% confidence interval (CI)] = 0.74 (0.58-0.95) for <2.5kg vs 3.9+kg, P for trend < 0.001; higher somatotype at age 5: HR=0.57 (95% CI 0.44-0.73) for 5-9 vs 1, P fortrend < 0.0001]; and at age 10: HR=0.61 (95% CI 0.49-0.75) for 5-9 vs 1, P for trend < 0.0001]; and BMI at age 18: HR=0.67 (95% 0.47-0.95) for ≥ 27.5 kg/m2 vs < 18.5 kg/m2, P for trend = 0.009], after adjusting for age and body fatness measures earlier in life and other risk factors, respectively. No significant interaction between body fatness measures was found. Women with the lowest birthweight, the highest somatotype at ages 5 and 10 and the highest BMI at age 18 and currently had a 72% (95% CI 54%-83%) lower incidence of invasive premenopausal breast cancer than women with the opposite extreme of each body fatness indicator. CONCLUSION The lowest incidence of premenopausal breast cancer was associated with the lowest birthweight and the highest childhood, adolescent and early adult body fatness.
Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl‐xL silenced glioma cell lines

Because the anti‐apoptotic protein Bcl‐xL is overexpressed in glioma, one might expect that inhibiting or silencing this gene would promote tumor cell killing. However, our studies have shown that this approach has limited independent activity, but may tip the balance in favor of apoptosis induction in response to other therapeutic interventions. To address this issue, we performed a pharmacological screen using a panel of signaling inhibitors and chemotherapeutic agents in Bcl‐xL silenced cells. Although limited apoptosis induction was observed with a series of inhibitors for receptor tyrosine kinases, PKC inhibitors, Src family members, JAK/STAT, histone deacetylase, the PI3K/Akt/mTOR pathway, MAP kinase, CDK, heat shock proteins, proteasomal processing, and various conventional chemotherapeutic agents, we observed a dramatic potentiation of apoptosis in Bcl‐xL silenced cells with the survivin inhibitor, YM155. Treatment with YM155 increased the release of cytochrome c, smac/DIABLO and apoptosis inducing‐factor, and promoted loss of mitochondrial membrane potential, activation of Bax, recruitment of LC3‐II to the autophagosomes and apoptosis in Bcl‐xL silenced cells. We also found an additional mechanism for the augmentation of apoptosis due to abrogation of DNA double‐strand break repair mediated by Rad51 repression and enhanced accumulation of γH2AX. In summary, our observations may provide a new insight into the link between Bcl‐xL and survivin inhibition for the development of novel therapies for glioma. © 2016 Wiley Periodicals, Inc.
Misremembering Past Affect Predicts Adolescents’ Future Affective Experience During Exercise

ABSTRACT Purpose: Increasing physical activity among adolescents is a public health priority. Because people are motivated to engage in activities that make them feel good, this study examined predictors of adolescents’ feelings during exercise. Method: During the 1st semester of the school year, we assessed 6th-grade students’ (N = 136) cognitive appraisals of the importance of exercise. Participants also reported their affect during a cardiovascular fitness test and recalled their affect during the fitness test later that semester. During the 2nd semester, the same participants rated their affect during a moderate-intensity exercise task. Results: Affect reported during the moderate-intensity exercise task was predicted by cognitive appraisals of the importance of exercise and by misremembering affect during the fitness test as more positive than it actually was. This memory bias mediated the association between appraising exercise as important and experiencing a positive change in affect during the moderate-intensity exercise task. Conclusion: These findings highlight the roles of both cognitive appraisals and memory as factors that may influence affect during exercise. Future work should explore whether affect during exercise can be modified by targeting appraisals and memories related to exercise experiences.