Miracle-dz/UniFAR-FTUs huggingface dataset:
Neprilysin Overexpression Inhibits Plaque Formation But Fails to Reduce Pathogenic Aβ Oligomers and Associated Cognitive Deficits in Human Amyloid Precursor Protein Transgenic Mice

The accumulation of amyloid-β (Aβ) peptides in the brain of patients with Alzheimer's disease (AD) may arise from an imbalance between Aβ production and clearance. Overexpression of the Aβ-degrading enzyme neprilysin in brains of human amyloid precursor protein (hAPP) transgenic mice decreases overall Aβ levels and amyloid plaque burdens. Because AD-related synaptic and cognitive deficits appear to be more closely related to Aβ oligomers than to plaques, it is important to determine whether increased neprilysin activity also diminishes the levels of pathogenic Aβ oligomers and related neuronal deficits in vivo. To address this question, we crossed hAPP transgenic mice with neprilysin transgenic mice and analyzed their offspring. Neprilysin overexpression reduced soluble Aβ levels by 50% and effectively prevented early Aβ deposition in the neocortex and hippocampus. However, it did not reduce levels of Aβ trimers and Aβ*56 or improve deficits in spatial learning and memory. The differential effect of neprilysin on plaques and oligomers suggests that neprilysin-dependent degradation of Aβ affects plaques more than oligomers and that these structures may form through distinct assembly mechanisms. Neprilysin's inability to prevent learning and memory deficits in hAPP mice may be related to its inability to reduce pathogenic Aβ oligomers. Reduction of Aβ oligomers will likely be required for anti-Aβ treatments to improve cognitive functions.
The Effect of Ambient Air Pollution on Sperm Quality

Background Research has suggested an association with ambient air pollution and sperm quality. Objectives We investigated the effect of exposure to ozone (O3) and particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) on sperm quality. Methods We reexamined a previous cohort study of water disinfection by-products to evaluate sperm quality in 228 presumed fertile men with different air pollution profiles. Outcomes included sperm concentration, total sperm per ejaculate (count), and morphology, as well as DNA integrity and chromatin maturity. Exposures to O3 and PM2.5 were evaluated for the 90–day period before sampling. We used multivariable linear regression, which included different levels of adjustment (i.e., without and with season and temperature) to assess the relationship between exposure to air pollutants during key periods of sperm development and adverse sperm outcomes. Results Sperm concentration and count were not associated with exposure to PM2.5, but there was evidence of an association (but not statistically significant) with O3 concentration and decreased sperm concentration and count. Additionally, a significant increase in the percentage of sperm cells with cytoplasmic drop [β = 2.64; 95% confidence interval (CI), 0.21–5.06] and abnormal head (β = 0.47; 95% CI, 0.03–0.92) was associated with PM2.5 concentration in the base model. However, these associations, along with all other sperm outcomes, were not significantly associated with either pollutant after controlling for season and temperature. Overall, although we found both protective and adverse effects, there was generally no consistent pattern of increased abnormal sperm quality with elevated exposure to O3 or PM2.5. Conclusions Exposures to O3 or PM2.5 at levels below the current National Ambient Air Quality Standards were not associated with statistically significant decrements in sperm outcomes in this cohort of fertile men. However, some results suggested effects on sperm concentration, count, and morphology.
Effect of secondary prehospital risk factors on outcome in severe traumatic brain injury in the context of fast access to trauma care.

BACKGROUND Prevention of secondary prehospital risk factors such as hypoxia and hypotension is likely to improve patient prognosis in severe traumatic brain injury (TBI). Because the Dutch trauma care organization is characterized by fast access to specialized trauma care due to the geographical situation, we investigated whether and to what extend secondary risk factors, such as hypoxia and hypotension, and measures, such as endotracheal intubation, affect outcome in severe TBI in the context of a region with fast access to trauma care. METHODS The medical records of 339 subsequent computed tomography-confirmed patients with TBI with a Glasgow coma scale (GCS) score≤8 who were primarily referred to a Level I trauma center in Amsterdam or Nijmegen in the Netherlands were retrospectively analyzed. RESULTS Multinomial logistic regression revealed that the strongest outcome predictors in our population were a disturbed pupillary reflex (odds ratio [OR], 5.8), a GCS score of 3 (OR, 4.9), and arterial hypotension (OR, 3.5). Interestingly, we observed no differences between intubated and nonintubated patients with respect to metabolic and respiratory parameters or mortality whereby the injury severity score was slightly higher in endotracheally intubated patients (32 [25-41]) versus nonintubated patients (25 [22-29]). CONCLUSION In agreement with others, GCS, a disturbed pupil reflex, and arterial hypotension were predictive for the prognosis of primarily referred patients with severe TBI in the Netherlands. In contrast, in the perspective of slightly higher injury scores in intubated patients, prehospital endotracheal intubation was not predictive for patient outcome.
Reproductive Biology and Endocrinology Open Access Cumulus Expansion, Nuclear Maturation and Connexin 43, Cyclooxygenase-2 and Fsh Receptor Mrna Expression in Equine Cumulus-oocyte Complexes Cultured in Vitro in the Presence of Fsh and Precursors for Hyaluronic Acid Synthesis

The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH) and precursors for hyaluronic acid synthesis. Equine cumulus-oocyte complexes (COC) were cultured in a control defined medium supplemented with eFSH (0 to 5 micrograms/ml), Fetal Calf Serum (FCS), precursors for hyaluronic acid synthesis or glutamine according to the experiments. After in vitro maturation, the cumulus expansion rate was increased with 1 microgram/ml eFSH, and was the highest with 20% FCS. It was not influenced by precursors for hyaluronic acid synthesis or glutamine. The expression of transcripts related to cumulus expansion was analyzed in equine cumulus cells before maturation, and after in vivo and in vitro maturation, by using reverse transcription-polymerase chain reaction (RT-PCR) with specific primers. Connexin 43, cyclooxygenase-2 (COX-2) and FSH receptor (FSHr) mRNA were detected in equine cumulus cells before and after maturation. Their level did not vary during in vivo or in vitro maturation and was influenced neither by FSH nor by precursors for hyaluronic acid synthesis. Results indicate that previously reported regulation of connexin 43 and COX-2 proteins during equine COC maturation may involve post-transcriptional mechanisms.
Long-term efficacy of psychological treatments for binge eating disorder.

BACKGROUND The long-term efficacy of psychological treatments for binge eating disorder remains largely unknown. AIMS To examine the long-term efficacy of out-patient group cognitive-behavioural therapy (CBT) and group interpersonal psychotherapy (IPT) for binge eating disorder and to analyse predictors of long-term non-response. METHOD Ninety people with binge eating disorder were assessed 4 years after treatment cessation within a randomised trial (trial registration: NCT01208272). RESULTS Participants showed substantial long-term recovery, partial remission, clinically significant improvement and significant reductions in associated psychopathology, despite relapse tendencies in single secondary outcomes. Body mass index remained stable. While the IPT group demonstrated an improvement in eating disorder symptoms over the follow-up period, the CBT group reported a worsening of symptoms, but treatments did not differ at any time point. CONCLUSIONS The results document the long-term efficacy of out-patient CBT and IPT for binge eating disorder. Further research is warranted to elucidate the time course and mechanisms of change of these treatments for binge eating disorder.
The Effect of Latent Toxoplasma gondii Infection on the Immune Response in HIV-Infected Patients

A relationship between latent toxoplasmosis and the immune system during HIV disease is poorly understood. Therefore, the aim of this follow-up study was to characterize immunological parameters in HIV-infected patients with latent toxoplasmosis and noninfected individuals. A total of 101 HIV-infected patients were enrolled in the study. The patients were classified into two groups based on anti-Toxoplasma gondii antibodies: a group of 55 toxoplasma-positive persons (TP) and a group of 46 toxoplasma-negative persons (TN). Absolute counts of several lymphocyte subsets decreased in the TP group, namely, T cells (p = 0.007), B cells (p = 0.002), NK cells (p = 0.009), CD4 T cells (p = 0.028), and CD8 T cells (p = 0.004). On the other hand, the percentage of CD8 T cells expressing CD38 and HLA-DR significantly increased during the follow-up in the TP group (p = 0.003, p = 0.042, resp.) as well as the intensity of CD38 and HLA-DR expression (MFI) on CD8 T cells (p = 0.001, p = 0.057, resp.). In the TN group, analysis of the kinetics of immunological parameters revealed no significant changes over time. In conclusion, the results suggest that latent T. gondii infection modulates the immune response during HIV infection.
Scaling of Brain Metabolism and Blood Flow in Relation to Capillary and Neural Scaling

Brain is one of the most energy demanding organs in mammals, and its total metabolic rate scales with brain volume raised to a power of around 5/6. This value is significantly higher than the more common exponent 3/4 relating whole body resting metabolism with body mass and several other physiological variables in animals and plants. This article investigates the reasons for brain allometric distinction on a level of its microvessels. Based on collected empirical data it is found that regional cerebral blood flow CBF across gray matter scales with cortical volume as , brain capillary diameter increases as , and density of capillary length decreases as . It is predicted that velocity of capillary blood is almost invariant (), capillary transit time scales as , capillary length increases as , and capillary number as , where is typically a small correction for medium and large brains, due to blood viscosity dependence on capillary radius. It is shown that the amount of capillary length and blood flow per cortical neuron are essentially conserved across mammals. These results indicate that geometry and dynamics of global neuro-vascular coupling have a proportionate character. Moreover, cerebral metabolic, hemodynamic, and microvascular variables scale with allometric exponents that are simple multiples of 1/6, rather than 1/4, which suggests that brain metabolism is more similar to the metabolism of aerobic than resting body. Relation of these findings to brain functional imaging studies involving the link between cerebral metabolism and blood flow is also discussed.
Using Ensemble Learners to Improve Classifier Performance on Tweet Sentiment Data

Sentiment analysis of tweets requires the ability to reliably and accurately identify the emotional polarity (positive or negative) of instances. This can be challenging, particularly when the data quality is questionable due to noise or imbalance. Ensemble learning algorithms have been shown to offer superior performance compared to non-ensemble techniques in many domains, but have not been thoroughly studied in the domain of tweet sentiment classification. In this work, we compare the performance of two popular ensemble techniques, bagging and boosting. Both bagging and boosting are tested using seven different base learners. Additionally, we compare the performance of ensemble techniques to using each of the base learners with no ensemble technique. Each of the resulting 21 learning algorithms is trained and tested on two datasets, a large automatically labeled lower quality dataset and a small manually labeled high quality dataset. We find that, in general, ensemble learners achieve higher performance on both datasets, and that bagging is superior when data quality is a concern.
Genetic Diversity of Intimin Genes of Attaching and Effacing Escherichia coli Strains

ABSTRACT In this study, we determined the sequences of four intimin variant genes detected in attaching and effacing Escherichia coli isolates of human origin. Three of them were novel and were designated eae-η (eta), eae-ι (iota), and eae-κ (kappa). The fourth was identical to the recently described eae-ζ (zeta), isolated from a bovine E. coli O84:NM isolate. We compared these sequences with those of published intimin-α, intimin-β, intimin-γ1, intimin-γ2, intimin-ε, and intimin-θ alleles. Sequence analysis of these 10 intimin alleles confirmed extensive genetic diversity within the intimin gene family in E. coli. The genetic diversity was more prominent in the 3′ region (starting at bp 2112), which encodes the binding domain of intimin. Phylogenetic analyses revealed four groups of closely related intimin genes: α and ζ; β and κ; γ1 and γ2/θ; and ε and η. Calculation of homoplasy ratios of sequences of the 5′ region of eae (positions 1 to 2111) revealed evidence for intragenic recombination. Split decomposition analysis also indicates that recombination events have played a role in the evolutionary history of eae. In conclusion, we recommend an eae nomenclature system based on the Greek alphabet and provide an updated PCR scheme for amplification and typing of E. coli eae.
Protein import through the nuclear pore complex is a multistep process

The transport of macromolecules across the nuclear envelope is mediated by the nuclear pore complex (NPC). Using cryo-electron microscopy and image processing we have mapped the interaction of three specific gold probes with the NPC and obtained projection maps of two possible intermediates in nuclear import. The probes used in these experiments were (a) mAb-414, which cross-reacts with Xenopus nucleoporins containing O-linked N-acetyl glucosamines; (b) wheat germ agglutinin, a transport inhibitor; and (c) nucleoplasmin, a transport substrate. Strong binding sites of the three probes are circularly arrayed on NPCs between radii of 100 and 125 A and may be coextensive. These results suggest that nucleoplasmin-gold (NP-gold) can form at least three distinct complexes with a central transport assembly of the NPC, which may represent intermediates of a multistep protein import pathway. Initially, NP-gold appears to bind at multiple sites located around the periphery of the closed NPC transporter and also directly over the center where it can dock. In a subsequent step NP-gold is translocated through the nuclear pore.
Kinetic Quantitation of Cerebral PET-FDG Studies Without Concurrent Blood Sampling: Statistical Recovery of the Arterial Input Function

Kinetic quantitation of dynamic positron emission tomography (PET) studies via compartmental modeling usually requires the time-course of the radio-tracer concentration in the arterial blood as an arterial input function (AIF). For human and animal imaging applications, significant practical difficulties are associated with direct arterial sampling and as a result there is substantial interest in alternative methods that require no blood sampling at the time of the study. A fixed population template input function derived from prior experience with directly sampled arterial curves is one possibility. Image-based extraction, including requisite adjustment for spillover and recovery, is another approach. The present work considers a hybrid statistical approach based on a penalty formulation in which the information derived from a priori studies is combined in a Bayesian manner with information contained in the sampled image data in order to obtain an input function estimate. The absolute scaling of the input is achieved by an empirical calibration equation involving the injected dose together with the subject's weight, height and gender. The technique is illustrated in the context of 18 F -Fluorodeoxyglucose (FDG) PET studies in humans. A collection of 79 arterially sampled FDG blood curves are used as a basis for a priori characterization of input function variability, including scaling characteristics. Data from a series of 12 dynamic cerebral FDG PET studies in normal subjects are used to evaluate the performance of the penalty-based AIF estimation technique. The focus of evaluations is on quantitation of FDG kinetics over a set of 10 regional brain structures. As well as the new method, a fixed population template AIF and a direct AIF estimate based on segmentation are also considered. Kinetics analyses resulting from these three AIFs are compared with those resulting from radially sampled AIFs. The proposed penalty-based AIF extraction method is found to achieve significant improvements over the fixed template and the segmentation methods. As well as achieving acceptable kinetic parameter accuracy, the quality of fit of the region of interest (ROI) time-course data based on the extracted AIF, matches results based on arterially sampled AIFs. In comparison, significant deviation in the estimation of FDG flux and degradation in ROI data fit are found with the template and segmentation methods. The proposed AIF extraction method is recommended for practical use.
A measured data set for evaluating electron-beam dose algorithms.

The purpose of this work was to develop an electron-beam dose algorithm verification data set of high precision and accuracy. Phantom geometries and treatment-beam configurations used in this study were similar to those in a subset of the verification data set produced by the Electron Collaborative Working Group (ECWG). Measurement techniques and quality-control measures were utilized in developing the data set to minimize systematic errors inherent in the ECWG data set. All measurements were made in water with p-type diode detectors and using a Wellhöfer dosimetry system. The 9 and 20 MeV, 15 x 15 cm2 beams from a single linear accelerator composed the treatment beams. Measurements were made in water at 100 and 110 cm source-to-surface distances. Irregular surface measurements included a "stepped surface" and a "nose-shaped surface. " Internal heterogeneity measurements were made for bone and air cavities in differing orientations. Confidence in the accuracy of the measured data set was reinforced by a comparison with Monte Carlo (MC)-calculated dose distributions. The MC-calculated dose distributions were generated using the OMEGA/BEAM code to explicitly model the accelerator and phantom geometries of the measured data set. The precision of the measured data, estimated from multiple measurements, was better than 0.5% in regions of low-dose gradients. In general, the agreement between the measured data and the MC-calculated data was within 2%. The quality of the data set was superior to that of the ECWG data set, and should allow for a more accurate evaluation of an electron beam dose algorithm. The data set will be made publicly available from the Department of Radiation Physics at The University of Texas M. D. Anderson Cancer Center.
[Comparison of clinical efficacy of heated humidified high flow nasal cannula versus nasal continuous positive airway pressure in treatment of respiratory distress syndrome in very low birth weight infants].

OBJECTIVE To compare the differences of clinical efficacy between heated humidified high-flow nasal cannula (HHHFNC) ventilation and nasal continuous positive airway pressure (NCPAP) in the treatment of respiratory distress syndrome (RDS) in very low birth weight (VLBW) infants. METHODS A total of 66 VLBW infants who were admitted to the neonatal intensive care unit were diagnosed with RDS, and they were randomly assigned to HHHFNC group and NCPAP group after receiving treatment with porcine pulmonary surfactant and conventional treatment. The changes in clinical symptoms and the incidence of complications were observed in the two groups. RESULTS The HHHFN group had significantly earlier first milk feeding and full enteral feeding, significantly shorter oxygen exposure time and invasive ventilation time, and significantly lower incidences of second intubation within 7 days, nasal injury, air leak, and abdominal distention, as compared with the NCPAP group. CONCLUSIONS Compared with NCPAP, HHHFNC causes slighter injury and has better tolerability, and it can be considered as the first choice of noninvasive ventilation in the treatment of RDS in VLBW infants.
Safety Transformation and the Structure of the Financial System

This paper studies how a financial system that is organized to efficiently create safe assets responds to macroeconomic shocks. Financial intermediaries face a cost of bearing risk, so they choose the least risky portfolio that backs their issuance of riskless deposits: a diversified pool of nonfinancial firms' debt. Nonfinancial firms choose their capital structure to exploit the resulting segmentation between debt and equity markets. Increased safe asset demand yields larger and riskier intermediaries and more levered firms. Quantitative easing reduces the size and riskiness of intermediaries and can decrease firm leverage, despite reducing borrowing costs at the zero lower bound.
The amino acid sequence of cytochrome c from Helix aspersa Müller (garden snail).

The amino acid sequence of a snail cytochrome c has been determined. The molecule consists of a single polypeptide chain of 104 residues, and is homologous with other mitochondrial cytochromes c. Unlike the cytochromes c from vertebrates, there is no acetyl blocking group at the N-terminus. A change in an otherwise invariant position has been observed in position 87. Comparison with amino acid sequences of cytochromes c from other sources indicates that the point of divergence of the molluscs and the vertebrates in evolutionary time was 720 million years ago. Experimental details are given in a supplementary paper that has been deposited as Supplementary Publication SUP 50009 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1972), 126, 5.