Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial.

OBJECTIVE To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women. DESIGN A 3-year, multicenter, randomized, double-blind, placebo-controlled trial. PARTICIPANTS A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy. INTERVENTION Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. PRIMARY ENDPOINTS: Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen. ANALYSIS Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment. RESULTS Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status. CONCLUSIONS Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia.
Of Mice and Men: Comparative Analysis of Neuro-Inflammatory Mechanisms in Human and Mouse Using Cause-and-Effect Models

Perturbance in inflammatory pathways have been identified as one of the major factors which leads to neurodegenerative diseases (NDD). Owing to the limited access of human brain tissues and the immense complexity of the brain, animal models, specifically mouse models, play a key role in advancing the NDD field. However, many of these mouse models fail to reproduce the clinical manifestations and end points of the disease. NDD drugs, which passed the efficacy test in mice, were repeatedly not successful in clinical trials. There are numerous studies which are supporting and opposing the applicability of mouse models in neuroinflammation and NDD. In this paper, we assessed to what extend a mouse can mimic the cellular and molecular interactions in humans at a mechanism level. Based on our mechanistic modeling approach, we investigate the failure of a neuroinflammation targeted drug in the late phases of clinical trials based on the comparative analyses between the two species.
Oxidative Stress Increased Respiration and Generation of Reactive Oxygen Species, Resulting in ATP Depletion, Opening of Mitochondrial Permeability Transition, and Programmed Cell Death1

Mitochondria constitute a major source of reactive oxygen species and have been proposed to integrate the cellular responses to stress. In animals, it was shown that mitochondria can trigger apoptosis from diverse stimuli through the opening of MTP, which allows the release of the apoptosis-inducing factor and translocation of cytochrome c into the cytosol. Here, we analyzed the role of the mitochondria in the generation of oxidative burst and induction of programmed cell death in response to brief or continuous oxidative stress in Arabidopsis cells. Oxidative stress increased mitochondrial electron transport, resulting in amplification of H2O2 production, depletion of ATP, and cell death. The increased generation of H2O2 also caused the opening of the MTP and the release of cytochromec from mitochondria. The release of cytochromec and cell death were prevented by a serine/cysteine protease inhibitor, Pefablock. However, addition of inhibitor only partially inhibited the H2O2 amplification and the MTP opening, suggesting that protease activation is a necessary step in the cell death pathway after mitochondrial damage.
Square root Kalman filtering for high-speed data received over fading dispersive HF channels

This paper shows how to apply square root Kalman filtering to high speed data transmission on fading dispersive high-frequency (HF) channels. High data-rate HF transmission can be achieved by use of a single carrier bandwidth efficiency modulation that is demodulated with decision-feedback equalization (DFE). The DFE coefficients are updated adaptively by square root Kalman algorithms. Theoretical formulation and mechanization procedures for the square root Kalman algorithms are given. Computer simulation indicates that good error-rate performance can be achieved with these algorithms for rapid fading HF radio channels.
Arctic sea surface height variability and change from satellite radar altimetry and GRACE, 2003-2014

Arctic sea surface height (SSH) is poorly observed by radar altimeters due to the poor coverage of the polar oceans provided by conventional altimeter missions and because large areas are perpetually covered by sea ice, requiring specialized data processing. We utilize SSH estimates from both the ice-covered and ice-free ocean to present monthly estimates of Arctic Dynamic Ocean Topography (DOT) from radar altimetry south of 81.5°N and combine this with GRACE ocean mass to estimate steric height. Our SSH and steric height estimates show good agreement with tide gauge records and geopotential height derived from Ice-Tethered Profilers. The large seasonal cycle of Arctic SSH (amplitude ∼5 cm) is dominated by seasonal steric height variation associated with seasonal freshwater fluxes, and peaks in October–November. Overall, the annual mean steric height increased by 2.2 ± 1.4 cm between 2003 and 2012 before falling to circa 2003 levels between 2012 and 2014 due to large reductions on the Siberian shelf seas. The total secular change in SSH between 2003 and 2014 is then dominated by a 2.1 ± 0.7 cm increase in ocean mass. We estimate that by 2010, the Beaufort Gyre had accumulated 4600 km3 of freshwater relative to the 2003–2006 mean. Doming of Arctic DOT in the Beaufort Sea is revealed by Empirical Orthogonal Function analysis to be concurrent with regional reductions in the Siberian Arctic. We estimate that the Siberian shelf seas lost ∼180 km3 of freshwater between 2003 and 2014, associated with an increase in annual mean salinity of 0.15 psu yr−1. Finally, ocean storage flux estimates from altimetry agree well with high-resolution model results, demonstrating the potential for altimetry to elucidate the Arctic hydrological cycle.
Costameres are sites of force transmission to the substratum in adult rat cardiomyocytes

Costameres, the vinculin-rich, sub-membranous transverse ribs found in many skeletal and cardiac muscle cells (Pardo, J. V., J. D. Siciliano, and S. W. Craig. 1983. Proc. Natl. Acad. Sci. USA. 80:363-367.) are thought to anchor the Z-lines of the myofibrils to the sarcolemma. In addition, it has been postulated that costameres provide mechanical linkage between the cells' internal contractile machinery and the extracellular matrix, but direct evidence for this supposition has been lacking. By combining the flexible silicone rubber substratum technique (Harris, A. K., P. Wild, and D. Stopak. 1980. Science (Wash. DC). 208:177-179. ) with the microinjection of fluorescently labeled vinculin and alpha-actinin, we have been able to correlate the distribution of costameres in adult rat cardiac myocytes with the pattern of forces these cells exert on the flexible substratum. In addition, we used interference reflection microscopy to identify areas of the cells which are in close contact to the underlying substratum. Our results indicate that, in older cell cultures, costameres can transmit forces to the extracellular environment. We base this conclusion on the following observations: (a) adult rat heart cells, cultured on the silicone rubber substratum for 8 or more days, produce pleat-like wrinkles during contraction, which diminish or disappear during relaxation; (b) the pleat-like wrinkles form between adjacent alpha-actinin-positive Z- lines; (c) the presence of pleat-like wrinkles is always associated with a periodic, "costameric" distribution of vinculin in the areas where the pleats form; and (d) a banded or periodic pattern of dark gray or close contacts (as determined by interference reflection microscopy) has been observed in many cells which have been in culture for eight or more days, and these close contacts contain vinculin. A surprising finding is that vinculin can be found in a costameric pattern in cells which are contracting, but not producing pleat-like wrinkles in the substratum. This suggests that additional proteins or posttranslational modifications of known costamere proteins are necessary to form a continuous linkage between the myofibrils and the extracellular matrix. These results confirm the hypothesis that costameres mechanically link the myofibrils to the extracellular matrix. We put forth the hypothesis that costameres are composite structures, made up of many protein components; some of these components function primarily to anchor myofibrils to the sarcolemma, while others form transmembrane linkages to the extracellular matrix.
Benchmark Dose Estimation Incorporating Multiple Data Sources

With the increased availability of toxicological hazard information arising from multiple experimental sources, risk assessors are often confronted with the challenge of synthesizing all available scientific information into an analysis. This analysis is further complicated because significant between‐source heterogeneity/lab‐to‐lab variability is often evident. We estimate benchmark doses using hierarchical models to account for the observed heterogeneity. These models are used to construct source‐specific and population‐average estimates of the benchmark dose (BMD). This is illustrated with an analysis of the U.S. EPA Region IX's reference toxicity database on the effects of sodium chloride on reproduction in Ceriodaphnia dubia. Results show that such models may effectively account for the lab‐source heterogeneity while producing BMD estimates that more truly reflect the variability of the system under study. Failing to account for such heterogeneity may result in estimates having confidence intervals that are overly narrow.
The place of spirometry in the diagnosis of asthma in those suffering from allergic rhinitis: a pilot study

Fontaine T, Laval JM, David B. Biochemical characterization and surfactant properties of horse allergens. Eur J Biochem 2001;268:3126–3136. 3. Gregoire C, Rosinski-Chupin I, Rabillon J, Alzari PM, David B, Dandeu JP. cDNA cloning and sequencing reveal the major horse allergen Ecu c1 to be a glycoprotein member of the lipocalin Superfamily. J Biological Chemistry 1996;271: 32951–32959. 4. Bulone V, Krogstad-Johnsen T, SmestadPaulsen B. Separation of horse dander allergen proteins by two-dimensional electrophoresis. Molecular characterization and identification of Equ c2.22101 and Equ c2.0102. Eur J Biochem 1998;253:202–211. 5. Dandeu JP, Rabillon J, Divanovic A, Carmı̀-Leroy A, David B. Hydrophobic interaction chromatography for isolation and purification of Equ c1, the horse major allergen. J Chromatography 1993;621: 23–31. 6. Virtanen T. Lipocalin allergens. Allergy 2001;56(Suppl 67):48–51.
Katanin maintains meiotic metaphase chromosome alignment and spindle structure in vivo and has multiple effects on microtubules in vitro

Caenorhabditis elegans bivalents are positioned between dense bundles of microtubules within female meiotic spindles. Rapid inactivation of katanin after meiotic spindle assembly causes loss of organized microtubule bundles and displacement of bivalents from the metaphase plate. Purified katanin can preferentially sever at intersections between microtubules.
Determination of Urinary Myo-/Chiro-Inositol Ratios from Korean Diabetes Patients

Of two major forms (myo- and chiro-inositol) of inositols, only chiro-inositol enhances the activity of proteins involved in intracellular glucose metabolism. This study aims to determine the urinary myo-/chiro-inositol ratio in type 1 and type 2 diabetes patients and compare its ratio with the normal control group. The 24-hour urinary myo- and chiro-inositols in 71 Korean diabetes patients and 39 control subjects have been quantified using high-performance liquid chromatography, and their ratios have been evaluated as indices of insulin resistance. The level of 24-hour urinary myo-inositol was significantly higher in both type 1 and type 2 diabetes than with the control group, whereas the urinary chiro-inositol in type 1 or type 2 diabetes was lower than that in normal subjects. The myo-/chiro-inositol ratio in diabetes patients was higher than that in the control group. Twenty four-hour urinary myo-/chiro-inositol ratios were significantly elevated in type 1 and type 2 diabetes patients compared to the control group, suggesting that a high ratio of urinary myo-/chiro-inositol in type 2 diabetes patients might be used for an index of insulin resistance.
Effect of egg yolk on growth of Mycobacterium tuberculosis in 7H12 liquid medium

Of 92 drug-resistant Mycobacterium tuberculosis strains isolated from sputum specimens, 86 showed growth in two types of 7H12 broth, one with egg yolk and the other without egg yolk. In addition, two strains grew only in plain 7H12 broth without yolk, and four others were recovered only in the medium supplemented with egg yolk. The radiometrically detected growth was higher in the presence of egg yolk, corresponding to a higher number of CFU per milliliter in these cultures. The improvement of growth in 7H12 broth supplemented with egg yolk was most noticeable in cultures isolated from sputum specimens having a low number of acid-fast bacilli in the smear and producing only a few colonies on solid media.
Robust Keystroke Biometric Anomaly Detection

The Keystroke Biometrics Ongoing Competition (KBOC) presented an anomaly detection challenge with a public keystroke dataset containing a large number of subjects and real-world aspects. Over 300 subjects typed case-insensitive repetitions of their first and last name, and as a result, keystroke sequences could vary in length and order depending on the usage of modifier keys. To deal with this, a keystroke alignment preprocessing algorithm was developed to establish a semantic correspondence between keystrokes in mismatched sequences. The method is robust in the sense that query keystroke sequences need only approximately match a target sequence, and alignment is agnostic to the particular anomaly detector used. This paper describes the fifteen best-performing anomaly detection systems submitted to the KBOC, which ranged from auto-encoding neural networks to ensemble methods. Manhattan distance achieved the lowest equal error rate of 5.32%, while all fifteen systems performed better than any other submission. Performance gains are shown to be due in large part not to the particular anomaly detector, but to preprocessing and score normalization techniques.
AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats

Ordered differential display identified a novel sequence induced in neurons by the neurite-promoting protein amphoterin. We named this gene amphoterin-induced gene and ORF (AMIGO), and also cloned two other novel genes homologous to AMIGO (AMIGO2 and AMIGO3). Together, these three AMIGOs form a novel family of genes coding for type I transmembrane proteins which contain a signal sequence for secretion and a transmembrane domain. The deduced extracellular parts of the AMIGOs contain six leucine-rich repeats (LRRs) flanked by cysteine-rich LRR NH2- and COOH-terminal domains and by one immunoglobulin domain close to the transmembrane region. A substrate-bound form of the recombinant AMIGO ectodomain promoted prominent neurite extension in hippocampal neurons, and in solution, the same AMIGO ectodomain inhibited fasciculation of neurites. A homophilic and heterophilic binding mechanism is shown between the members of the AMIGO family. Our results suggest that the members of the AMIGO protein family are novel cell adhesion molecules among which AMIGO is specifically expressed on fiber tracts of neuronal tissues and participates in their formation.
Globalization of Continuing Professional Development by Journal Clubs via Microblogging: A Systematic Review

Background Journal clubs are an essential tool in promoting clinical evidence-based medical education to all medical and allied health professionals. Twitter represents a public, microblogging forum that can facilitate traditional journal club requirements, while also reaching a global audience, and participation for discussion with study authors and colleagues. Objective The aim of the current study was to evaluate the current state of social media–facilitated journal clubs, specifically Twitter, as an example of continuing professional development. Methods A systematic review of literature databases (Medline, Embase, CINAHL, Web of Science, ERIC via ProQuest) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of Twitter, the followers of identified journal clubs, and Symplur was also performed. Demographic and monthly tweet data were extracted from Twitter and Symplur. All manuscripts related to Twitter-based journal clubs were included. Statistical analyses were performed in MS Excel and STATA. Results From a total of 469 citations, 11 manuscripts were included and referred to five Twitter-based journal clubs (#ALiEMJC, #BlueJC, #ebnjc, #urojc, #meded). A Twitter-based journal club search yielded 34 potential hashtags/accounts, of which 24 were included in the final analysis. The median duration of activity was 11.75 (interquartile range [IQR] 19.9, SD 10.9) months, with 7 now inactive. The median number of followers and participants was 374 (IQR 574) and 157 (IQR 272), respectively. An overall increasing establishment of active Twitter-based journal clubs was observed, resulting in an exponential increase in total cumulative tweets (R 2=.98), and tweets per month (R 2=.72). Cumulative tweets for specific journal clubs increased linearly, with @ADC_JC, @EBNursingBMJ, @igsjc, @iurojc, and @NephJC, and showing greatest rate of change, as well as total impressions per month since establishment. An average of two tweets per month was estimated for the majority of participants, while the “Top 10” tweeters for @iurojc showed a significantly lower contribution to overall tweets for each month (P<.005). A linearly increasing impression:tweet ratio was observed for the top five journal clubs. Conclusions Twitter-based journal clubs are free, time-efficient, and publicly accessible means to facilitate international discussions regarding clinically important evidence-based research.
An automatic corpus based method for a building Multiple Fuzzy Word Dataset

Fuzzy sentence semantic similarity measures are designed to be applied to real world problems where a computer system is required to assess the similarity between human natural language and words or prototype sentences stored within a knowledge base. Such measures are often developed for a specific corpus/domain where a limited set of words and sentences are evaluated. As new “fuzzy” measures are developed the research challenge is on how to evaluate them. Traditional approaches have involved rigorous and complex human involvement in compiling benchmark datasets and obtaining human similarity measures. Existing datasets often contain limited fuzzy words and do allow the fuzzy measures to be exhaustively tested. This paper presents an automatic method for the generation of a Multiple Fuzzy Word Dataset (MFWD) from a corpus. A Fuzzy Sentence Pairing Algorithm is used to extract and augment high, medium and low similarity sentence pairs with multiple fuzzy words. Human ratings are collected through crowdsourcing and the MFWD is evaluated using both fuzzy and traditional sentence similarity measures. The results indicated that fuzzy measures returned a higher correlation with human ratings compared with traditional measures.
Effects of GABRA2 Variation on Physiological, Psychomotor and Subjective Responses in the Alcohol Challenge Twin Study

Abstract Multiple reports have identified variation in the GABRA2 gene as contributing to the genetic susceptibility to alcohol dependence. However, both the mechanism behind this association, and the range of alcohol-related phenotypes affected by variation in this gene, are currently undefined. Other data suggest that the risk of alcohol dependence is increased by relative insensitivity to alcohol's intoxicating effects. We have therefore tested whether GABRA2 variation is associated with variation in the subjective and objective effects of a standard dose of alcohol in humans. Data on responses to alcohol from the Alcohol Challenge Twin Study (Martin et al., 1985) have been tested against allelic and haplotype information obtained by typing 41 single-nucleotide polymorphisms in or close to the GABRA2 gene. Nominally significant allelic associations (p < .05, without correction for multiple testing) were found for body sway, motor coordination, pursuit rotor and arithmetical computation tasks, and for the personality dimension of Neuroticism. Because of the large number of phenotypes tested, these possibly significant findings will need to be confirmed in further studies.
Maternal psychological morbidity and low birth weight in India

Summary Depression following childbirth is associated with poor child growth in developing countries. We describe the association between psychological morbidity during pregnancy and low birth weight (<2.5 kg). A cohort of 270 mothers was recruited from a district hospital in Goa, India; all mothers were interviewed with a screening questionnaire for psychological morbidity. Babies of 250 mothers were reviewed at birth to measure their weight. Excluding 5 premature babies, we found that maternal psychological morbidity was independently associated with low birth weight (odds ratio 1.44, 95% CI 1.00–2.07). We conclude that maternal psychological morbidity has an adverse impact on foetal growth.