Miracle-dz/UniFAR-FTUs huggingface dataset:
Aspirin use and mortality from cancer in a prospective cohort study.

UNLABELLED There is evidence that use of aspirin offers several potential health benefits including cancer prevention and cardiovascular disease prevention. The purpose of this study was to assess the association between aspirin use and death from cancer and cardiovascular diseases with a special emphasis on cancer mortality. MATERIALS AND METHODS The baseline data for this prospective cohort study were collected in 1971--1975 for the first National Health and Nutrition Examination Study (NHANES I) and 1976--1980 as part of the second NHANES (NHANES II) with mortality follow-up using the National Death Index (NDI) through December 31, 1992. The main analyses were the relative risks of total mortality and cause-specific mortality for persons who used aspirin compared to persons who did not use aspirin adjusted for confounding using Cox proportional hazards. RESULTS The proportion of aspirin users was lower among cancer cases than non-cases (58% versus 66%) and use of aspirin decreased with age. Consequently, age was a negative confounder attenuating the protective association between aspirin use and cancer and cardiovascular mortality. After adjusting for age, BMI, sex, race, poverty index, education and smoking, we observed a significant association of reduced all cause mortality among all aspirin users (relative risk [RR] = 0.88; 95% confidence interval [CI] 0.85 - 0.99) and lung cancer mortality among male aspirin users (RR = 0.69; CI 0.49-0.96). However, for women we observed adverse associations between aspirin use and bladder (RR=12.31; CI 2.98-50.80) and brain cancer mortality (RR=3.13; CI 1.09-9.00), although case numbers were small. CONCLUSION Aspirin use appears to offer protection from all causes of mortality and lung cancer among men. In women aspirin use is associated with increased risk of bladder and brain cancer. Because of the small number of female bladder (n=15) and brain (n=20) cancer cases in this cohort the findings require confirmation.
Constitutive modelling of branched polymer melts in non-linear response

This thesis is concerned with modelling long chain branched polymer melts using the McLeish and Larson Pompom constitutive equations. Usually the non-linear terms in this model are fitted to uniaxial extensional data due its sensitivity to levels of branching, but in this thesis I will study a number of other non-linear flows using this model. For each flow the results are compared to experiments on a set of polyethylene melts. The first flow types I examine are simple shear flows. In a shear step-strain flow the stress relaxation of branched polymers is observed to be time-strain separable, whereby the relaxation modulus can be separated into the product of separate functions of time and strain. I show that although the Pompom model is not time-strain separable in general, there exist subsets of parameter values for which time-strain separability is valid. For these sets a branched damping function is derived which is analogous to the Doi-Edwards damping function for linear polymer melts. The other simple shear flow examined is oscillatory shear. Commonly, oscillatory shear is probed at low strain amplitudes over a range of frequencies to measure the usual dynamic moduli of linear viscoelasticity. In this work the effect of strain amplitude is explored up to absolute strains of order unity. The non-linear stress response is analysed from the higher harmonics in the Fourier series. In particular it is shown that the third Fourier components are dependent on the Pompom non-linear stretch relaxation time and a low-strain asymptote is obtained. Subsequently, this thesis focuses on the stagnation point flow generated in a cross-slot geometry. The stress calculated from the Pompom constitutive model is compared to experimental flow induced birefringence images. It is shown for linear and lightly branched materials that the Pompom model predicts both the form of the birefringence pattern and stress values obtained from the stress-optical law. However, for more highly branched polymers the Pompom model fails to predict the change to birefringence patterns. Subsequent analysis shows that there could exist a transient overshoot in extension which the Pompom model cannot capture as it stands. In the final part of my thesis I suggest an empirical alteration to the Pompom constitutive model to capture this transient extensional overshoot, which is able to resolve the differences between experimental flow induced birefringence images and theoretical simulations.
Concomitant Ankle Injuries Associated With Tibial Shaft Fractures

Background: Ankle injuries associated with tibial shaft fractures can cause postoperative ankle pain and stiffness even when satisfactory bony union has been achieved. Although several previous studies have described these injuries, they have not been clearly defined or classified in terms of ankle injury type or need for surgical fixation. Methods: Seventy-one consecutive patients (mean ± SD age, 48.3 ± 16.7 years; 37 men and 34 women) with tibial shaft fractures who underwent computed tomography examination were included. Data were collected including age, sex, body mass index, fracture location of the tibia and fibula (in percentile of length), tibial fracture shape (spiral, oblique, transverse), presence and pattern of concomitant ankle injuries (on the distal tibial articular surface), and necessity for surgical fixation of ankle injuries. Factors associated with concomitant ankle injuries associated with tibial shaft fractures were analyzed by logistic regression analysis. Results: A total of 47 (64.7%) of the 71 tibial shaft fractures involved concomitant ankle injuries, including 8 cases of combined lateral malleolar fracture, posterior malleolar fracture, and anterior inferior tibiofibular ligament (AITFL) avulsion fracture; 9 cases of combined posterior malleolar fracture and AITFL avulsion fracture; 6 cases of combined lateral malleolar fracture and posterior malleolar fracture; 1 case of combined lateral malleolar fracture and AITFL avulsion fracture; 10 cases of posterior malleolar fracture; 7 cases of lateral malleolar fracture; 5 cases of AITFL avulsion fracture; and 1 unclassified fracture. Of these, 34 of the ankle injuries required surgical fixation. Spiral-type tibial shaft fracture was significantly associated with concomitant ankle injury (P = .001). Conclusions: Orthopaedic surgeons should be aware that tibial shaft fractures, especially spiral-type fractures, are frequently associated with ankle injuries, such as lateral malleolar fractures, posterior malleolar fractures, and AITFL avulsion fractures. A considerable portion of these cases may necessitate surgical fixation. We recommend all spiral-type tibial shaft fractures routinely undergo computed tomography examination. Level of Evidence: Level III, comparative series.
Reduced expression levels of let-7c in human breast cancer patients

Circulating microRNAs (miRNAs) are important in the diagnosis of a number of diseases, since serum or plasma miRNAs are more stable compared with miRNA isolated from blood samples. The aim of the present study was to investigate the association between the expression levels of serum let-7c miRNA and the clinical diagnosis of breast cancer (BC). The circulating let-7c levels of 90 BC patients and 64 healthy controls were determined by performing a reverse transcription-quantitative polymerase chain reaction assay. The results demonstrated that let-7c expression was downregulated in the BC tissues compared with the paracarcinoma control tissues. In addition, the let-7c expression in the serum of BC patients was significantly lower compared with the healthy controls (P<0.01). Using a cutoff value of 0.374×103 copies/ml, the serum expression levels of let-7c exhibited 87.5% sensitivity and 78.9% specificity for distinguishing BC patients from healthy controls (area under the receiver operating characteristic curve, 0.848; 95% confidence interval, 0.785–0.911). Furthermore, the results demonstrated that the serum expression levels of let-7c were significantly higher in premenopausal compared with postmenopausal patients (P<0.05), supporting the hypothesis that postmenopausal status may affect the serum expression levels of let-7c. However, no statistically significant differences were detected in the serum levels of let-7c between ER (or PR)-positive and -negative patients. Therefore, the current study hypothesized that serum let-7c may be used as a novel and valuable biomarker for the diagnosis of BC.
Metabiotics: novel idea or natural development of probiotic conception

Traditionally, probiotics are live microorganisms that are considered to be both beneficial and safe. Unfortunately, their effects may be short-lived, inconsequential, or ambiguous. Some symbiotic (probiotic) microorganisms with known health benefits may cause opportunistic infections, increase incidence of allergic sensitization and autoimmune disorders, produce microecological imbalance, modify gene expression, transfer genes that are virulent and resistant to antibiotics, cause disorders in epigenome and genome integrity, induce chromosomal DNA damage, and activate signaling pathways associated with cancer and other chronic diseases. As of now, the commercially available probiotics serve as a first-generation means of correcting microecological disorders. Further development will include the selection of natural metabiotics and/or formulation of synthetic (or semi-synthetic) metabiotics that will be analogies or improvised versions of natural bioactives, produced by symbiotic (probiotic) microorganisms. Metabiotics are structural components of probiotic microorganisms and/or formulation of and/or signaling molecules with a determined (known) chemical structure that can optimize host-specific physiological functions and regulate metabolic and/or behavior reactions connected with the activity of host indigenous microbiota. Metabiotics are advantageous because of their chemical structure, dosage, safety, and long shelf-life. Thus, metabiotics should not be considered a myth; they are the result of the natural evolution of probiotic conception.
The nutritionally responsive transcriptome of the polyphenic beetle Onthophagus taurus and the importance of sexual dimorphism and body region

Developmental responses to nutritional variation represent one of the ecologically most important classes of adaptive plasticity. However, knowledge of genome-wide patterns of nutrition-responsive gene expression is limited. Here, we studied genome-wide transcriptional responses to nutritional variation and their dependency on trait and sex in the beetle Onthophagus taurus. We find that averaged across the transcriptome, nutrition contributes less to overall variation in gene expression than do sex or body region, but that for a modest subset of genes nutrition is by far the most important determinant of expression variation. Furthermore, our results reject the hypothesis that a common machinery may underlie nutrition-sensitive development across body regions. Instead, we find that magnitude (measured by number of differentially expressed contigs), composition (measured by functional enrichment) and evolutionary consequences (measured by patterns of sequence variation) are heavily dependent on exactly which body region is considered and the degree of sexual dimorphism observed on a morphological level. More generally, our findings illustrate that studies into the developmental mechanisms and evolutionary consequences of nutrition-biased gene expression must take into account the dynamics and complexities imposed by other sources of variation in gene expression such as sexual dimorphism and trait type.
Spectroscopy of New High Proper Motion Stars in the Northern Sky. I. New Nearby Stars, New High-Velocity Stars, and an Enhanced Classification Scheme for M Dwarfs

We define an enhanced spectral classification scheme for M dwarf stars and use it to derive spectral classification of 104 northern stars with proper motions larger than 0. ″5 yr-1 that we discovered in a survey of high proper motion stars at low Galactic latitudes. The final tally is as follows: 54 M dwarfs, 25 sdK and sdM subdwarfs, 14 esdK and esdM extreme subdwarfs, and 11 DA and DC white dwarfs. Among the most interesting cases, we find one star to be the coolest subdwarf ever reported (LSR 2036+5059, with spectral type sdM7.5), a new M9.0 dwarf only about 6 pc distant (LSR 1835+3259), and a new M6.5 dwarf only 7 pc from the Sun (LSR 2124+4003). Spectroscopic distances suggests that 27 of the M dwarfs, three of the white dwarfs, and one of the subdwarfs (LSR 2036+5059) are within 25 pc of the Sun, making them excellent candidates for inclusion in the solar neighborhood census. Estimated sky-projected velocities suggest that most of our subdwarfs and extreme subdwarfs have halo kinematics. We find that several white dwarfs and non–metal-poor M dwarfs also have kinematics consistent with the halo, and we briefly discuss their possible origin.
A MODEL FOR A COMPREHENSIVE ASSESSMENT OF EXPOSURE AND LIFETIME CANCER INCIDENCE RISK FROM PLUTONIUM RELEASED FROM THE ROCKY FLATS PLANT, 1953–1989

A model was developed to calculate ambient air concentrations, surface deposition, and lifetime carcinogenic risk with uncertainty from plutonium released to the air from the Rocky Flats Plant between the years 1953 and 1989. The model integrated airborne release estimates and atmospheric dispersion and deposition calculations from 37 years of routine plant operations and episodic releases. Episodic releases included two major fires in 1957 and 1969 that breached the building air filtration systems, and suspension of plutonium contaminated soil from the former 903 waste storage area during high winds. Predicted air concentrations included contributions from site releases and resuspension from contaminated soil. Inhalation was the only exposure pathway considered. Environmental measurements suitable for model validation were lacking for the period when major site releases occurred (1953 to 1970). However, environmental media, such as soil and lake sediment, are natural accumulators and provided evidence of past offsite releases. The geometric mean predicted-to-observed (P/O) ratio for soil was 0.93 with a geometric standard deviation of 1.6. The model systematically underpredicted concentrations near the 903 Area because large, nonrespirable particles that deposited close to the source were not included in release estimates. Plutonium soil inventories for the model domain had P/O ratios ranging from 0.22 to 4.2. The geometric mean P/O ratio for ambient air was 0.90 with a geometric standard deviation of 2.6. Age-dated sediment cores from Standley Lake had a geometric mean P/O ratio of 1.0 with a geometric standard deviation of 1.7. Predicted-to-observed ratios for plutonium inventories in Great Western Reservoir ranged from 0.36 to 1.7. Lifetime cancer incidence risks were calculated for a male laborer scenario who resided in the model domain for the entire assessment time. Maximum cancer risks ranged from 10−6 (5th percentile) to 10−4 (95th percentile). Most of the exposure was incurred during the 1950’s.
Optical Identification of the Hardest X-Ray Source in the ASCA Large Sky Survey

We report the optical identification of the hardest X-ray source (AX J131501+3141) detected in an unbiased wide-area survey in the 0.5-10 keV band, the ASCA Large Sky Survey (LSS). The X-ray spectrum of the source is very hard and is well reproduced by a power-law component (Γ=1.5−0.6+0.7) with NH=6−2+4×1022 cm-2. We have found a galaxy with R = 15.62 mag near the center of the error circle for the X-ray source. The optical spectrum of the galaxy shows only narrow emission lines whose ratios correspond to those of a type 2 Seyfert galaxy at z = 0.072, implying an absorption-corrected X-ray luminosity of 2 × 1043 ergs s-1 (2-10 keV) and MB = -20.93 mag. A radio point source is also associated with the center of the galaxy. We thus identify the X-ray source with this galaxy as an obscured active galactic nucleus (AGN). The hidden nature of the nucleus of the galaxy in the optical band is consistent with the X-ray spectrum. These results support the idea that the obscured AGNs/QSOs contribute significantly to the cosmic X-ray background in the hard band at the faint flux level.
Unsupervised learning of temporal features for word categorization in a spiking neural network model of the auditory brain

The nature of the code used in the auditory cortex to represent complex auditory stimuli, such as naturally spoken words, remains a matter of debate. Here we argue that such representations are encoded by stable spatio-temporal patterns of firing within cell assemblies known as polychronous groups, or PGs. We develop a physiologically grounded, unsupervised spiking neural network model of the auditory brain with local, biologically realistic, spike-time dependent plasticity (STDP) learning, and show that the plastic cortical layers of the network develop PGs which convey substantially more information about the speaker independent identity of two naturally spoken word stimuli than does rate encoding that ignores the precise spike timings. We furthermore demonstrate that such informative PGs can only develop if the input spatio-temporal spike patterns to the plastic cortical areas of the model are relatively stable. Author Summary Currently we still do not know how the auditory cortex encodes the identity of complex auditory objects, such as words, given the great variability in the raw auditory waves that correspond to the different pronunciations of the same word by different speakers. Here we argue for temporal information encoding within neural cell assemblies for representing auditory objects. Unlike the more traditionally accepted rate encoding, temporal encoding takes into account the precise relative timing of spikes across a population of neurons. We provide support for our hypothesis by building a neurophysiologically grounded spiking neural network model of the auditory brain with a biologically plausible learning mechanism. We show that the model learns to differentiate between naturally spoken digits “one” and “two” pronounced by numerous speakers in a speaker-independent manner through simple unsupervised exposure to the words. Our simulations demonstrate that temporal encoding contains significantly more information about the two words than rate encoding. We also show that such learning depends on the presence of stable patterns of firing in the input to the cortical areas of the model that are performing the learning.
Analysis of Adhesion Molecules and Basement Membrane Contributions to Synaptic Adhesion at the Drosophila Embryonic NMJ

Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributions come from the extracellular matrix and its receptors. Most of these factors have been scrutinised by loss-of-function analyses in animal models. However, which adhesion factors establish the essential physical links across synaptic clefts and allow the assembly of synaptic machineries at the contact site in vivo is still unclear. To investigate these key questions, we have used the neuromuscular junction (NMJ) of Drosophila embryos as a genetically amenable model synapse. Our ultrastructural analyses of NMJs lacking different classes of CAMs revealed that loss of all neurexins, all classical cadherins or all glutamate receptors, as well as combinations between these or with a Laminin deficiency, failed to reveal structural phenotypes. These results are compatible with a view that these CAMs might have no structural role at this model synapse. However, we consider it far more likely that they operate in a redundant or well buffered context. We propose a model based on a multi-adaptor principle to explain this phenomenon. Furthermore, we report a new CAM-independent adhesion mechanism that involves the basement membranes (BM) covering neuromuscular terminals. Thus, motorneuronal terminals show strong partial detachment of the junction when BM-to-cell surface attachment is impaired by removing Laminin A, or when BMs lose their structural integrity upon loss of type IV collagens. We conclude that BMs are essential to tie embryonic motorneuronal terminals to the muscle surface, lending CAM-independent structural support to their adhesion. Therefore, future developmental studies of these synaptic junctions in Drosophila need to consider the important contribution made by BM-dependent mechanisms, in addition to CAM-dependent adhesion.
Bioactive Compounds and Biological Activities of Jatropha curcas L. Kernel Meal Extract

Defatted Jatropha curcas L. (J. curcas) seed kernels contained a high percentage of crude protein (61.8%) and relatively little acid detergent fiber (4.8%) and neutral detergent fiber (9.7%). Spectrophotometric analysis of the methanolic extract showed the presence of phenolics, flavonoids and saponins with values of 3.9, 0.4 and 19.0 mg/g DM, respectively. High performance liquid chromatography (HPLC) analyses showed the presence of gallic acid and pyrogallol (phenolics), rutin and myricetin (flavonoids) and daidzein (isoflavonoid). The amount of phorbol esters in the methanolic extract estimated by HPLC was 3.0 ± 0.1 mg/g DM. Other metabolites detected by GC-MS include: 2-(hydroxymethyl)-2 nitro-1,3-propanediol, β-sitosterol, 2-furancarboxaldehyde, 5-(hydroxymethy) and acetic acid in the methanolic extract; 2-furancarboxaldehyde, 5-(hydroxymethy), acetic acid and furfural (2-furancarboxaldehyde) in the hot water extract. Methanolic and hot water extracts of kernel meal showed antimicrobial activity against both Gram positive and Gram negative pathogenic bacteria (inhibition range: 0–1.63 cm) at the concentrations of 1 and 1.5 mg/disc. Methanolic extract exhibited antioxidant activities that are higher than hot water extract and comparable to β-carotene. The extracts tended to scavenge the free radicals in the reduction of ferric ion (Fe3+) to ferrous ion (Fe2+). Cytotoxicity assay results indicated the potential of methanolic extract as a source of anticancer therapeutic agents toward breast cancer cells.
Stimulation of Ca2+‐independent exocytosis in rat pituitary gonadotrophs by G‐protein

1 We employed the whole‐cell recording technique in conjunction with fluorometry to measure cytosolic Ca2+ concentration ([Ca2+]i) and exocytosis (capacitance measurement) in single, identified rat gonadotrophs. 2 Direct activation of G‐protein (via intracellular dialysis of non‐hydrolysable analogues of GTP, but not of GDP) triggered a slow rise in capacitance even in the presence of a fast intracellular Ca2+ chelator. 3 The broad‐spectrum kinase inhibitors H7 and staurosporine did not prevent this Ca2+‐independent exocytosis, ruling out the involvement of the cAMP and PKC pathways. 4 AlF4−, a potent stimulator of heterotrimeric G‐proteins, failed to stimulate any exocytosis when the intracellular Ca2+ store was depleted, implicating the involvement of AlF4−‐insensitive G‐protein(s). 5 Maximal stimulation of Ca2+‐independent exocytosis by GTP analogues did not reduce the number of readily releasable granules that were available subsequently for Ca2+‐dependent release. 6 The last finding raises the possibility that the G‐protein‐stimulated Ca2+‐independent exocytosis may regulate a pool of granules that is distinct from the Ca2+‐dependent pool.