Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal changes in testosterone over five years in community-dwelling men.

CONTEXT There are few population-based studies reporting longitudinal changes in total T, LH, FSH, and SHBG levels, and there is limited information on risk factors for their change. OBJECTIVE The objective of the study was to examine 5-year changes in serum T, LH, FSH, and SHBG levels among Australian men. DESIGN The study initially included a randomly selected, community-based cohort of 1588 men age 35 years or older at recruitment (mean age, 54 ± 11 y) with available data at 2 visits. Men on medications known to affect, or with established pathology of, the hypothalamo-pituitary gonadal axis were excluded, leaving 1382 for analysis. RESULTS Mean baseline and follow-up T levels were 16.2 ± 1.4 and 15.6 ± 1.4 nmol/L, a change of -0.13 nmol/L/y. Annualized T changes were associated with obesity, being unmarried, and smoking at baseline, but not with diabetes, hypertension, or cardiovascular disease. T declined in men who had persistent depression or developed chronic disease, and it increased in men who were married, as compared to unmarried, at both time points. In the multivariate analysis, smoking cessation, development of central obesity (waist ≥ 100 cm), or generalized obesity (body mass index ≥ 30 kg/m(2)) resulted in T decreases of 0.36, 0.25, and 0.20 nmol/L/y, respectively. Quitting smoking, developing obesity, and having persisting depression were inversely related to SHBG change. CONCLUSIONS An age-related decline in T levels is not inevitable but is largely explained by smoking behavior and intercurrent changes in health status, particularly obesity and depression.
Anger and anxiety in borderline hypertension.

&NA; Psychologic studies of hypertension have usually focused on the relationship of anger and anxiety to clinic or laboratory blood pressure (BP). Yet, average blood pressure outside of the clinic has proven to be a more important predictor of hypertensive complications. In this study, we have isolated two groups of borderline hypertensives—one group that maintained high blood pressure outside of the clinic and another whose average BP returned to normal at home. All 33 subjects were given psychometric instruments for measuring various components of anger and anxiety: Spielberger's State‐Trait Personality Inventory, the Anger Expression Scale, and the State Anger Reaction Scale. The high home BP group reported greater intensity of anger, although they suppressed their expression of anger to a greater extent. The groups did not differ in anxiety. Also, blood pressure variability was not different between the two groups. It is suggested that the psychologic differences found in the group of higher‐risk borderline hypertensives may, through autonomic arousal, contribute to the later development of established hypertension.
Selection and placement of oral ventilation tubes based on tracheal morphometry

Evidence‐based guidelines for the selection of appropriately sized ventilation tubes as well as their placement do not exist, although iatrogenic injuries to the trachea and larynx following endotracheal intubation are not infrequent. Our objective was to provide selection recommendations for ventilation tubes based on anatomic criteria.
WT1 Induction of Mitogen-Activated Protein Kinase Phosphatase 3 Represents a Novel Mechanism of Growth Suppression

In its role as a tumor suppressor, WT1 transactivates several genes that are regulators of cell growth and differentiation pathways. For instance, WT1 induces the expression of the cell cycle regulator p21, the growth-regulating glycoprotein amphiregulin, the proapoptotic gene Bak, and the Ras/mitogen-activated protein kinase (MAPK) inhibitor Sprouty1. Here, we show that WT1 transactivates another important negative regulator of the Ras/MAPK pathway, MAPK phosphatase 3 (MKP3). In a WT1-inducible cell line that exhibits decreased cell growth and increased apoptosis on expression of WT1, microarray analysis showed that MKP3 is the most highly induced gene. This was confirmed by real-time PCR where MKP3 and other members of the fibroblast growth factor 8 syn expression group, which includes Sprouty 1 and the Ets family of transcription factors, were induced rapidly following WT1 expression. WT1 induction was associated with a block in the phosphorylation of extracellular signal-regulated kinase in response to epidermal growth factor stimulation, an effect mediated by MKP3. In the presence of a dominant-negative MKP3, WT1 could no longer block phosphorylation of extracellular signal-regulated kinase. Lastly, when MKP3 expression is down-regulated by short hairpin RNA, WT1 is less able to block Ras-mediated transformation of 3T3 cells. (Mol Cancer Res 2008;6(7):1225–31)
Adding insult to injury: care of patients with acute kidney injury.

Acute kidney injury, formerly known as acute renal failure, is both a prevalent and serious problem among hospitalized patients. Although no definitive studies have been undertaken in the UK the prevalence among inpatients in the USA is 4.9% (Waikar et al, 2007). Associated mortality rates have been wide ranging.
Non-uniform vowel normalization

A study of female-male differences in F F2: and F3 of var ious vowels within eight different languages revea ls univer sa l tendencies of departure f rom a simple uniform scaling. These have been quantified and adopted a s a basis for a vowel-category-specific normalization procedure which, on the average, reduces the female-male variance to one-half of that remaining after a simple uniform scaling of the type suggested by Nordstrom and Lindblom (paper 212 presented a t the 8th International Congress of Phonetic Sciences, Leeds 1975). Dialectal variations within a speaker group a r e thus of the same order of magnitude a s a universal pattern of deviations f rom a simple scale factor. P a r t s of this pattern can be ascr ibed to non-uniform scaling of vocalt r ac t dimensions. Other p a r t s requi re the assumption of sexspecific articulation which may have developed to satisfy per ceptual c r i te r ia . I t i s interesting to note that the scaling of tenor formants versus bass singers ' formants a r e s imilar to the female-male scaling (demonstrated by Tom Cleveland in a forthcoming paper).
ATTRACTING DYNAMICS OF EXPONENTIAL MAPS

We give a complete classiflcation of hyperbolic components in the space of iterated exponential maps z7! ‚ exp(z) , and we describe a preferred parametrization of those components. More precisely, we associate to every hyperbolic component of period n a flnite symbolic sequence of length ni 1 , we show that every such sequence is realized by a hyperbolic component, and the hyperbolic component specifled by any such sequence is unique. This leads to a complete classiflcation of all exponential maps with attracting dynamics, which is a fundamental step in the understanding of exponential parameter space.
Deeply Supervised Salient Object Detection with Short Connections

Recent progress on saliency detection is substantial, benefiting mostly from the explosive development of Convolutional Neural Networks (CNNs). Semantic segmentation and saliency detection algorithms developed lately have been mostly based on Fully Convolutional Neural Networks (FCNs). There is still a large room for improvement over the generic FCN models that do not explicitly deal with the scale-space problem. Holisitcally-Nested Edge Detector (HED) provides a skip-layer structure with deep supervision for edge and boundary detection, but the performance gain of HED on saliency detection is not obvious. In this paper, we propose a new saliency method by introducing short connections to the skip-layer structures within the HED architecture. Our framework provides rich multi-scale feature maps at each layer, a property that is critically needed to perform segment detection. Our method produces state-of-the-art results on 5 widely tested salient object detection benchmarks, with advantages in terms of efficiency (0.08 seconds per image), effectiveness, and simplicity over the existing algorithms.
The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy

Purpose: Hypoxic ischemic encephalopathy (HIE) accounts for 60% of all neonatal seizures. There is emerging evidence that seizures cause additional injury to the developing brain that has sustained hypoxic ischemic injury. Temporal evolution of clinical seizure burden in HIE has been characterized, with maximum clinical seizure burden (the period of maximum seizure activity) being observed between 12 and 24 h of age. The purpose of our study was to investigate the distribution of electrographic seizure burden (the accumulated duration of seizures over a defined time period), following the initial hypoxic ischemic insult.
Vitiligo presentation in adults

The characteristics of vitiligo in 41 adults presenting to a university dermatology clinic in Sheffield, UK were studied in a case review. Of 41 patients, 29 women and 12 men, there were 37 European Caucasians, three Asian Caucasians and one black African. Symmetrical and acrofacial types of vitiligo predominated but there were no segmental cases. Age of onset was before 20 years in 17, with a mean of 28 years; the oldest onset was 74 years. The average duration of the disease was 16 years. Autoimmune thyroid disease was present in 14 cases (34%). Only seven (18%) gave a family history of vitiligo. A precipitating factor was identified in nine (22%), including pregnancy, sunburn and skin trauma. Topical steroid treatment was given in 33 and narrow-band ultraviolet B was prescribed in nine. This series is unusual in having no cases of segmental vitiligo, perhaps because no children are included, and in having a high prevalence of thyroid disease.
GRB 050904 at redshift 6.3: observations of the oldest cosmic explosion after the Big Bang

We present optical and near-infrared observations of the afterglow of the gamma-ray burst GRB 050904. We derive a photometric redshift z = 6.3, estimated from the presence of the Lyman break falling between the I and J filters. This is by far the most distant GRB known to date. Its isotropic-equivalent energy is 3.4 × 10 53 erg in the rest-frame 110−1100 keV energy band. Despite the high redshift, both the prompt and the afterglow emission are not peculiar with respect to other GRBs. We find a break in the J-band light curve at tb = 2.6 ± 1.0 d (observer frame). If we assume this is the jet break, we derive a beaming-corrected energy Eγ ∼ (4 ÷ 12) × 10 51 erg. This limit shows that GRB 050904 is consistent with the Amati and Ghirlanda relations. This detection is consistent with the expected number of GRBs at z > 6 and shows that GRBs are a powerful tool to study the star formation history up to very high redshift.
Function of the exon 7 deletion variant estrogen receptor alpha protein in an estradiol-resistant, tamoxifen-sensitive human endometrial adenocarcinoma grown in nude mice.

BACKGROUND In addition to hormone and DNA binding, interactions, including competition with other proteins, appear to be a critical component of transcriptional regulation by the estrogen receptor alpha (ER(alpha)). In vitro studies suggest that exon deletion (Delta exon) variant forms of ER(alpha) may also play an important role in determining the progression from hormone dependence to hormone independence in receptor positive tumors. METHODS We investigated the presence of ERalpha mRNA and protein variants and their possible role in a moderately differentiated human endometrial adenocarcinoma grown in nude mice. In addition to wild-type (wt), RT-PCR assay of the tumor revealed the presence of two mRNA variants, a low concentration of Delta5 and a high concentration of Delta7 ER(alpha). We detected wt, Delta7, and Delta5,7 mRNA by sequencing the transcripts after stable transfection of three HeLa cells with either splice variant. The linked in vitro translation/transcription assay of the transfected cells and the Western blot analysis of the original tumor generated both wt (66 kDa) and Delta7 (52 kDa), Delta5,7 (46 kDa) ER(alpha) proteins. RESULTS Tumor growth was characterized as estradiol and progesterone resistant but tamoxifen sensitive, i.e., neither estradiol nor progesterone treatment altered the growth rate, whereas tamoxifen treatment significantly increased the tumor volume doubling time. Estradiol treatment decreased the wt and increased the Delta7 variant ER(alpha) protein expression significantly in a dose-dependent manner. Tamoxifen treatment, however, increased the expression of both proteins whereas progesterone had no effect. Estradiol treatment did not influence expression of the Delta5,7 variant protein, which increased significantly in the tamoxifen-treated tumors. Gel mobility shift assays revealed that both wt and Delta7 ER(alpha) proteins bind to the consensus DNA sequence, whereas the Delta5,7 variant protein did not. CONCLUSIONS We conclude that estradiol, tamoxifen, and progesterone regulate wt and variant ER(alpha) mRNA and protein expression separately and differently and that this hormonal regulation probably occurs, via different mechanisms, at the transcriptional or posttranscriptional level. The Delta7 variant ER(alpha) may play a crucial role in the determination of hormone sensitivity and thus in the outcome of hormone treatment of human endometrial adenocarcinomas.
Forgotten fungi—the gut mycobiome in human health and disease

The human body is home to a complex and diverse microbial ecosystem that plays a central role in host health. This includes a diversity of fungal species that is collectively referred to as our 'mycobiome'. Although research into the mycobiome is still in its infancy, its potential role in human disease is increasingly recognised. Here we review the existing literature available on the human mycobiota with an emphasis on the gut mycobiome, including how fungi interact with the human host and other microbes. In doing so, we provide a comprehensive critique of the methodologies available to research the human mycobiota as well as highlighting the latest research findings from mycological surveys of different groups of interest including infants, obese and inflammatory bowel disease cohorts. This in turn provides new insights and directions for future studies in this burgeoning research area.
Dynamic modelling and stability analysis of articulated frame steer vehicles

The stability analysis of articulated frame steer vehicle models is presented. To reveal the relationship between the 'oversteer' and 'jack-knife' motion modes based on a 2 degree of freedom (DOF) and 3 DOF vehicle models, respectively, the results derived from these models are investigated and compared. To identify the effects of design variables on the lateral stability of the vehicle, a more realistic model with a hydraulic rotary valve and dynamic tyre models is generated on the basis of the 3 DOF model and the results derived from these models are examined and compared. Similar to traditional articulated vehicles, the jack-knife and 'snaking' modes were identified from practical operations of the articulated frame steer vehicles. Results demonstrate that, with the decrease of the angular spring (representing the hydraulic cylinder between the front and rear sections of the vehicle) stiffness coefficient, the oversteer mode evolves into the jack-knife mode. Compared with the static tyre model, the effects of dynamic transient lateral tyre force degrades the stability of the vehicle over the lower speed range. Results also illustrate that, with the fluid leakage either in the rotary valve or in the hydraulic cylinder, the stability of the oversteer mode dominated motion degrades. On the contrary, in the case of snaking mode dominated motion, the introduction of the fluid leakage will improve the stability of the vehicles.
BOT FLY PARASITISM (ROGENHOFERA BONAERENSIS) (DIPTERA, CUTEREBRIDAE) IN THE PAMPEAN GRASSLAND MOUSE (AKODON AZARAE), IN ARGENTINA

Seasonality and impact of parasitism by the larvae of Rogenhofera bonaerensis (Diptera: Cuterebridae) in pampean grassland mouse (Akodon azarae, Rodentia, Cricetidae) populations were studied in grasslands and cropfield borders near Diego Gaynor (Buenos Aires Province, Argentina), from November 1985 to December 1986. Trapped mice infections ranged from one larva (77%) to four (4%) per host; larvae occured on tails (75.7%), backs (17.1%), thighs (5.7%), and abdomen (1.4%). Prevalence of larvae occurred in late spring (November and December) (35%), and in fall (March to June) (20%), with a peak of 25% during April and May. In spring these larvae affected 46% of resident and 19% of transient individuals; however, no differences were found between residents and transients in spring or fall. There was no significant relationship between mouse population density and prevalence of parasitism (r = −0.56). The annual percentage of infected rodents changed with age (body size classes): adults (37%) > subadults (25%) > juveniles (16%); with no differences between the sexes. Similar results were recorded in the spring, but there were no differences in the fall. Significant differences were not detected between stable (22% infected) and disturbed habitats (14% infected). During winter uninfected mice survived better than those infected during the previous fall. In contrast, the summer survival among spring infected mice and noninfected mice was similar. Parasitism showed no effects on reproductive activity and on home range size. Larvae showed strong host specificity for A. azarae (99%). Only one case was recorded in the long-tailed mouse (Oligoryzomys flavescens), and none in the white paunch mouse (Calomys laucha), both species sympatric with A. azarae. This suggests that the pampean grassland mouse is essential for perpetuation of this bot fly as a result of a coevolutionary process within the grassland rodent assemblage. According to the A. azarae population dynamics the bot fly strategy could be adjusted to an opportunist pattern.
Distinct Activation Properties of the Nuclear Factor of Activated T-cells (NFAT) Isoforms NFATc3 and NFATc4 in Neurons*♦

Background: Ca2+/calcineurin-dependent transcription factor NFAT regulates many neuronal functions. Results: Depolarization/Ca2+ influx-induced activation and nuclear translocation are markedly faster and stronger for NFATc3 than NFATc4 in neurons, which is determined in part by SP-containing regions of NFATc3 and NFATc4. Conclusion: Activation of NFATc3 and NFATc4 is distinctly regulated in neurons. Significance: The distinct regulation of NFATc3 and NFATc4 may underlie isoform-specific NFAT functions in neurons. The Ca2+/calcineurin-dependent transcription factor NFAT (nuclear factor of activated T-cells) is implicated in regulating dendritic and axonal development, synaptogenesis, and neuronal survival. Despite the increasing appreciation for the importance of NFAT-dependent transcription in the nervous system, the regulation and function of specific NFAT isoforms in neurons are poorly understood. Here, we compare the activation of NFATc3 and NFATc4 in hippocampal and dorsal root ganglion neurons following electrically evoked elevations of intracellular Ca2+ concentration ([Ca2+]i). We find that NFATc3 undergoes rapid dephosphorylation and nuclear translocation that are essentially complete within 20 min, although NFATc4 remains phosphorylated and localized to the cytosol, only exhibiting nuclear localization following prolonged (1–3 h) depolarization. Knocking down NFATc3, but not NFATc4, strongly diminished NFAT-mediated transcription induced by mild depolarization in neurons. By analyzing NFATc3/NFATc4 chimeras, we find that the region containing the serine-rich region-1 (SRR1) mildly affects initial NFAT translocation, although the region containing the serine-proline repeats is critical for determining the magnitude of NFAT activation and nuclear localization upon depolarization. Knockdown of glycogen synthase kinase 3β (GSK3β) significantly increased the depolarization-induced nuclear localization of NFATc4. In contrast, inhibition of p38 or mammalian target of rapamycin (mTOR) kinases had no significant effect on nuclear import of NFATc4. Thus, electrically evoked [Ca2+]i elevation in neurons rapidly and strongly activates NFATc3, whereas activation of NFATc4 requires a coincident increase in [Ca2+]i and suppression of GSK3β, with differences in the serine-proline-containing region giving rise to these distinct activation properties of NFATc3 and NFATc4.
The causal effect of educational attainment on Alzheimer’s disease: A two-sample Mendelian randomization study

Background Observational evidence suggests that higher educational attainment is protective for Alzheimer’s disease (AD). It is unclear whether this association is causal or confounded by demographic and socioeconomic characteristics. We examined the causal effect of educational attainment on AD in a two-sample MR framework. Methods We extracted all available effect estimates of the 74 single nucleotide polymorphisms (SNPs) associated with years of schooling from the largest genome-wide association study (GWAS) of educational attainment (N=293,723) and the GWAS of AD conducted by the International Genomics of Alzheimer’s Project (n=17,008 AD cases and 37,154 controls). SNP-exposure and SNP-outcome coefficients were combined using an inverse variance weighted approach, providing an estimate of the causal effect of each SD increase in years of schooling on AD. We also performed appropriate sensitivity analyses examining the robustness of causal effect estimates to the various assumptions and conducted simulation analyses to examine potential survival bias of MR analyses. Findings With each SD increase in years of schooling (3.51 years), the odds of AD were, on average, reduced by approximately one third (odds ratio= 0.63, 95% confidence interval [CI]: 0.48 to 0.83, p<0.001). Causal effect estimates were consistent when using causal methods with varying MR assumptions or different sets of SNPs for educational attainment, lending confidence to the magnitude and direction of effect in our main findings. There was also no evidence of survival bias in our study. Interpretation Our findings support a causal role of educational attainment on AD, whereby an additional ∼3.5 years of schooling reduces the odds of AD by approximately one third.
ASSESSMENT OF KNOWLEDGE, ATTITUDE AND PRACTICE (KAP) OF COMMUNITY TOWARD RABIES IN MEDAWELABU DISTRICT, BALE ZONE, ETHIOPIA

The study was conducted in Meda Welabu district, Bale zone, Ethiopia from March 2019 to November 2019 to assess the knowledge, attitude and practice of the community toward rabies using a community based cross sectional study supported by semi-structured questionnaire survey. Meda Welabu district and the kebeles were selected purposively and by lottery method respectively, while the households from each kebeles were selected using systematic random sampling technique. Of 400 people interviewed, the majority of participants (88%) had been heard of rabies previously and 52.5% of them knew dogs as the reservoir of rabies. About 73% of them answered bite is the major source of rabies transmission and 62.8% could able to describe the symptoms of rabies in dogs. Statistically significant difference was revealed between some key questions related to KAP and explanatory variables like sex (P<0.001), age (P<0.001) educational levels (P<0.001) and religion (P<0.001) of respondents. Generally, the people in this area are a little bit known about rabies; however, they have negative attitude and practice on rabies. Therefore, an education outreach should be conveyed to ensure accurate knowledge, improve attitude and practice about rabies in this area.