Miracle-dz/UniFAR-FTUs huggingface dataset:
Performance of a Statistical Model to Predict Stroke Outcome in the Context of a Large, Simple, Randomized, Controlled Trial of Feeding

Background and Purpose— Statistical models to predict the outcome of stroke patients have several uses. Their utility depends on their predictive accuracy in patients other than those on whom they were developed (ie, external validity). We sought to test the external validity of some recently described models in patients enrolled in the FOOD (Feed Or Ordinary Diet) trial: a large randomized trial evaluating feeding policies in patients with stroke. Methods— The predictive variables were collected during a telephone call to randomize the patient a median of 5 days after stroke onset. Patients were followed up 6 months later to establish their survival, functional status, and residence. Charts were plotted to demonstrate the discrimination and calibration of the models. Results— The models performed well in the first 2955 patients enrolled and followed up in the FOOD trial. The area under the receiver operating characteristic curves varied between 0.78 and 0.81 (with 0.5 indicating no discrimination and 1.0 indicating perfect discrimination). The discrimination was marginally better for patients enrolled within the first day of stroke than later. The models tended to provide rather pessimistic predictions in all groups except those predicted to have a high likelihood of surviving free of dependency. Conclusions— As one might predict, the discriminatory power in the selected cohort of trial patients was marginally less good than in previously studied unselected cohorts used to test their external validity. These models provide a well-tested tool for stratification in trials, comparing outcomes in different cohorts and examining the additional predictive power of novel factors.
Measurement of the Inner Retinal Layers of Megalopapilla by Optical Coherence Tomography

The main purpose of this study was to assess the differences in the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses between subjects with megalopapilla (MP) and those with large (physiological) cup discs (LCD) measured by spectral-domain optical coherence tomography. The secondary purpose was to determine whether pRNFL and GCIPL thicknesses increase with the optic nerve head (ONH) area. This cross-sectional study included 184 eyes (92 eyes with MP and 92 eyes with LCD). The subjects with LCD were used as sex-and-age-matched controls. All subjects were imaged using the Cirrus HD-OCT system. Macula and pRNFL thickness maps were obtained for all subjects. The inferior quadrant pRNFL thickness was higher in the MP group than in the LCD group (P < 0.05). There were no differences in the GCIPL thickness between the two groups. A positive correlation was found between average, superior, and inferior quadrant pRNFL thicknesses and the ONH area (P < 0.05). The slope of the correlation curve was higher for the inferior quadrant. No correlation was found between the GCIPL thickness and the ONH area. In comparison to patients with LCD, the inferior quadrant pRNFL thickness of patients with MP was higher. As the ONH area increased, the average, superior, and inferior quadrant pRNFL thicknesses also increased. In patients with MP, the assessment of a glaucomatous lesion based on pRNFL thickness measurements may not be reliable. It is recommended that in these patients, the evaluation of glaucomatous damage be based on the GCIPL thickness map analysis rather than on the pRNFL thickness.
Cultural adaptation and validation of the Persian version of the Arthritis Impact Measurement Scales 2-Short Form in patients with osteoarthritis of the knee

Purpose. To translate and validate the Persian version of the Arthritis Measurement Scales 2-Short Form (AIMS2-SF) in patients with osteoarthritis (OA) of the knee. Method. The translation and cultural adaptation of the original questionnaire was carried out in accordance with published guidelines. One hundred and fourteen consecutive Persian-speaking patients with OA of the knee were participated in this study. The Short Form Health Survey (SF-36) and visual analogue scales (VAS) for pain and joint stiffness were used to test convergent validity of the Persian AIMS2-SF. In addition, 35 randomly selected patients were asked to complete the questionnaire 3 days later for the second time. Results. The Persian AIMS2-SF showed statistically significant good convergent validity, as assessed with the relevant subscales of the Persian SF-36 and VAS for pain and joint stiffness. Cronbach's alpha coefficient for the Persian AIMS2-SF components ranged from 0.68 to 0.80. The Persian AIMS2-SF components showed good to excellent test–retest reliability with intraclass correlation coefficient ranged from 0.72 to 0.83 (p < 0.01). Conclusions. The Persian version of the AIMS2-SF is a reliable and valid instrument to measure functional disability and health-related quality of life in patients with OA of the knee in Iran. It is simple and easy to use and now can be applied in clinical settings and future outcome studies in Iran.
Ventromedial Hypothalamic Mediation of Photoperiodic Gonadal Responses in Male Syrian Hamsters

Short day lengths induce testicular regression in seasonally breeding Syrian hamsters. To test whether the ventromedial hypothalamus is necessary to maintain reproductive quiescence once testicular regression has been achieved, photoregressed male hamsters were subjected to lesions of the ventromedial hypothalamus (VMHx), pinealectomy (Pinx), or sham operation (Sham). VMHx hamsters underwent accelerated gonadal recrudescence compared to Pinx and Sham hamsters. Recovery of prolactin concentrations (PRL) to values characteristic of long-day hamsters was hastened in the VMHx animals compared to Sham hamsters. Concentrations of follicle stimulating hormone (FSH) increased prematurely in both the VMHx and Pinx animals, beginning a few weeks after surgery.By the time the gonads had undergone recrudescence and the hamsters were refractory to melatonin, PRL and FSH concentrations had returned to baseline long-day values in all groups; there was no evidence of hypersecretion of either hormone in any of the animals with lesions. Melatonin concentrations of VMHx hamsters did not differ from those of sham-operated animals, but because only a single determination was made, it remains possible that VMH damage altered the duration of nightly melatonin secretion. An intact VMH appears to be essential for the continued maintenance of reproductive suppression induced by exposure to short day lengths; these and earlier findings suggest that the VMH-dorsomedial hypothalamic complex mediates regression of the reproductive apparatus during decreasing day lengths of late summer and early autumn and also is necessary to sustain regression during the winter months.
A p r 2 0 0 7 On the dragging of light by a rotating medium By

When light is passing through a rotating medium the optical polarisation is rotated. Recently it has been reasoned that this rotation applies also to the transmitted image (Padgett et al. 2006). We examine these two phenomena by extending an analysis of Player (1976) to general electromagnetic fields. We find that in this more general case the wave equation inside the rotating medium has to be amended by a term which is connected to the orbital angular momentum of the light. We show that optical spin and orbital angular momentum account respectively for the rotation of the polarisation and the rotation of the transmitted image.
Performance analysis of joint pairing and mode selection in D2D communications with FD radios

In cellular-D2D networks, users can select the communication mode either direct and form D2D links or indirect and communicate with BS. In former case, users should perform pairing selection and choose their pairs. The main focus in this paper is proposing an analytical framework by using tools from stochastic geometry to address these two issues, i.e. i) mode selection for the user devices to be established in either cellular or D2D mode, which is done based on received power from BS influenced by a bias factor, and ii) investigation of choosing nth-nearest neighbor as the serving node for the receiver of interest, by considering full-duplex (FD) radios as well as half-duplex (HD) in the D2D links. The analytic and simulation results demonstrate that even though the bias factor determines the throughput of each mode, it does not have any influence on the system sum throughput. Furthermore, we demonstrate that despite of suffering from self-interference, FD-D2D results in higher system sum throughput as well as higher coverage probability in comparison to its counterpart, namely purely HD-D2D network.
Neonatal Leptin Administration Alters Regional Brain Volumes and Blocks Neonatal Growth Restriction-Induced Behavioral and Cardiovascular Dysfunction in Male Mice

Premature delivery is often complicated by neonatal growth restriction (GR) and neurodevelopmental impairment. Because global overnutrition increases the risk of adult metabolic syndrome, we sought a targeted intervention. Premature delivery and perinatal GR decrease circulating levels of the neurotrophic hormone leptin. We hypothesized that leptin supplementation would normalize the outcomes of mice with incipient neonatal GR. Pups were fostered into litters of 6 or 12 to elicit divergent growth patterns. Pups in each litter received injections of saline or leptin from d 4 to 14. At 4 mo, mice underwent tail cuff blood pressure measurement, behavioral testing, and MRI. Mice fostered in litters of 12 had decreased weanling weights and leptin levels. Neonatal leptin administration normalized plasma leptin levels without influencing neonatal growth. Leptin replacement also normalized the hypertension, stress-linked immobility, conditioned fear, and amygdala enlargement seen in neonatal growth restricted male mice. In control males, neonatal leptin administration led to hypothalamic enlargement, without overt neurocardiovascular alterations. Female mice were less susceptible to the effects of neonatal GR or leptin supplementation. In conclusion, the effects of neonatal leptin administration are modulated by concurrent growth and gender. In growth restricted male mice, physiologic leptin replacement improves adult neurocardiovascular outcomes.
Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding

Centrosomes have recently emerged as key regulators of the cell cycle. The G1/S transition requires a functional centrosome, and centrosomal localization of numerous proteins, including cyclin/Cdk complexes, is important for the G2/M transition. Here we identify a modular centrosomal localization signal (CLS) localizing cyclin A to centrosomes independently of Cdk binding. The cyclin A CLS is located in a distinct part of the molecule compared with the cyclin E CLS and includes the MRAIL hydrophobic patch involved in substrate recognition. The cyclin A CLS interacts with p27KIP1, and expression of p27KIP1 removes cyclin A but not cyclin E from centrosomes. Expression of the cyclin A CLS displaces both endogenous cyclin A and E from centrosomes and inhibits DNA replication, supporting an emerging concept that DNA replication is linked to centrosomal events. Structural analysis indicates that differences in surface charge and length of the C-terminal helix explain why the MRAIL region in cyclin E is not a functional CLS. These results indicate that the cyclin A CLS may contribute to targeting and recognition of centrosomal Cdk substrates and is required for specific effects of p27KIP1 on cyclin A-Cdk2.
The validity of self-reported diagnosis of rheumatoid arthritis: results from a population survey followed by clinical examinations.

OBJECTIVE Self-reported diagnoses of rheumatic conditions are frequently used in epidemiological and clinical research. Our objectives were to examine the validity of patient self-reported rheumatoid arthritis (RA); and to assess the predictive value of symptoms, health status measures, and demographic variables with respect to the actual diagnosis. METHODS A postal survey was performed in Oslo of 10,000 randomly selected individuals between 20 and 79 years of age. Respondents reported musculoskeletal pain, stiffness, rheumatic diagnoses, disability, and mental distress. The patients reporting RA (either according to patient or doctor) were selected for further examination. RESULTS Of 5886 respondents (3670 with musculoskeletal pain or stiffness) 158 patients (2.7%) reported having RA diagnosed by doctor (n = 107) and/or according to their own opinion (n = 142). RA was confirmed by clinical examination in 35 of these 158 individuals (22%, CI 16,29). Patients with perceived and actual RA differed regarding self-reported presence of swollen joints and disability score. Multivariate analyses failed to identify a set of useful predictors for the correct diagnosis. CONCLUSION Patient self-reported diagnosis of RA is unreliable for research or clinical purposes.
Adrenocortical carcinoma and pregnancy: clinical and biological features and prognosis.

OBJECTIVE Adrenocortical carcinoma (ACC) is a rare, severe disease. Pregnancy-associated ACC has rarely been reported. We wished to evaluate the characteristics and prognosis of ACC diagnosed in patients during pregnancy or in the postpartum period, comparing them with those for ACC diagnosed in nonpregnant women. DESIGN Clinical presentation, hormonal secretion, staging, survival, and obstetric data are reported. Patients were included between 1963 and 2007. Mean follow-up was 48 months. PATIENTS AND METHODS This is a retrospective cohort study carried out at a referral center. All female patients aged 16-49 years diagnosed with ACC during the observation period were included (n=110). Twelve of these women were pregnant or in the first 6 months after delivery. Hormonal secretion, staging, obstetric data, and survival were analyzed. For the survival analysis, pregnant patients were compared with a subgroup of nonpregnant women matched for age, stage, and year of diagnosis (1 pregnant patient/2 controls). RESULTS Adrenocortical tumors diagnosed during pregnancy or in the postpartum period tend to be more often cortisol-secreting tumors (P=0.06) and to be discovered at a more advanced stage than those in nonpregnant women, although the differences were not significant. Fetal outcome was poor. Overall survival of the mother was worse than that of matched controls (hazard ratio of death: 3.98, confidence interval=1.34-11.85, P=0.013). CONCLUSION ACC diagnosed during pregnancy or in the postpartum period is associated with a poor fetal outcome and a poorer prognosis than ACC diagnosed in nonpregnant women.
Targeted Deletion of mek5 Causes Early Embryonic Death and Defects in the Extracellular Signal-Regulated Kinase 5/Myocyte Enhancer Factor 2 Cell Survival Pathway

ABSTRACT To elucidate the physiological significance of MEK5 in vivo, we have examined the effect of mek5 gene elimination in mice. Heterozygous mice appear to be healthy and were fertile. However, mek5− / − embryos die at approximately embryonic day 10.5 (E10.5). The phenotype of the mek5 − / − embryos includes abnormal cardiac development as well as a marked decrease in proliferation and an increase in apoptosis in the heart, head, and dorsal regions of the mutant embryos. The absence of MEK5 does not affect cell cycle progression but sensitizes mouse embryonic fibroblasts (MEFs) to the ability of sorbitol to enhance caspase 3 activity. Further studies with mek5 − / − MEFs indicate that MEK5 is required for mediating extracellular signal-regulated kinase 5 (ERK5) activation and for the regulation of the transcriptional activity of myocyte enhancer factor 2. Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development.
Elevated intraocular pressure and pseudoexfoliation of the lens capsule as risk factors for chronic open‐angle glaucoma

Abstract In 1984‐86, a glaucoma survey was carried out in a municipality in central Sweden, comprising 760 subjects 65–74 years of age. Since 1988, a follow‐up study of those 527 subjects who had normal and reliable visual fields has been in progress. A visual field defect was required for a diagnosis of chronic open‐angle glaucoma. By December 1991, 10 cases of capsular glaucoma and 3 cases of chronic simple glaucoma had been found. The standardized relative risk for chronic open‐angle glaucoma was 3.4 times (95% confidence interval: 1.1 ‐ 11) greater in subjects with a baseline intraocular pressure < 21 mmHg, using the highest pressure in either eye, than in those with an intraocular pressure < 21 mmHg. Pseudoexfoliation increased the standardized relative risk 9.8‐fold (95% confidence interval: 2.5 – 38). There was indication of effect modification between intraocular pressure and pseudoexfoliation. Optic disc haemorrhages were associated with a 4.8‐fold (95% confidence interval: 0.63 – 37) increased unadjusted risk. The study supports the pressure theory of optic nerve damage in glaucoma. Pseudoexfoliation was recognized as an independent risk factor for the development of chronic open‐angle glaucoma.
An Extension of RE-AIM to Enhance Sustainability: Addressing Dynamic Context and Promoting Health Equity Over Time

RE-AIM is a widely adopted, robust implementation science (IS) framework used to inform intervention and implementation design, planning, and evaluation, as well as to address short-term maintenance. In recent years, there has been growing focus on the longer-term sustainability of evidence-based programs, policies and practices (EBIs). In particular, investigators have conceptualized sustainability as the continued health impact and delivery of EBIs over a longer period of time (e.g., years after initial implementation) and incorporated the complex and evolving nature of context. We propose a reconsideration of RE-AIM to integrate recent conceptualizations of sustainability with a focus on addressing dynamic context and promoting health equity. In this Perspective, we present an extension of the RE-AIM framework to guide planning, measurement/evaluation, and adaptations focused on enhancing sustainability. We recommend consideration of: (1) extension of “maintenance” within RE-AIM to include recent conceptualizations of dynamic, longer-term intervention sustainability and “evolvability” across the life cycle of EBIs, including adaptation and potential de-implementation in light of changing and evolving evidence, contexts, and population needs; (2) iterative application of RE-AIM assessments to guide adaptations and enhance long-term sustainability; (3) explicit consideration of equity and cost as fundamental, driving forces that need to be addressed across RE-AIM dimensions to enhance sustainability; and (4) use or integration of RE-AIM with other existing frameworks that address key contextual factors and examine multi-level determinants of sustainability. Finally, we provide testable hypotheses and detailed research questions to inform future research in these areas.
Fungal Histidine Kinases

Eukaryotic cells predominantly use serine, threonine, and tyrosine phosphorylation in various intracellular signal transduction pathways. In contrast, prokaryotic organisms employ numerous "two-component" systems, in which signaling is achieved by transferring a phosphoryl group from phosphohistidine in the "sensor kinase" component to aspartate in the "response regulator" component. In the last several years, genetic screens and genome projects have identified sensor kinases and response regulators in lower eukaryotes and plants, revealing that eukaryotic organisms also make use of His-Asp phosphotransfer in a limited number of signaling pathways. Extensive studies in yeasts have demonstrated that a variation of the two-component system, a multistep "phosphorelay," is the prevailing mechanism among distantly related yeast species. In the budding yeast Saccharomyces cerevisiae, a His-Asp-His-Asp phosphorelay transmits osmotic stress signals to a mitogen-activated protein kinase (MAPK) cascade to induce adaptive responses. A phosphorelay in the fission yeast Schizosaccharomyces pombe, analogous to the S. cerevisiae phosphorelay, is responsible for MAPK activation in response to peroxide stress. Mammalian cells do not have any two-component or phosphorelay systems, although protein histidine kinases unrelated to the sensor kinase may be involved in cellular signaling. Because some phosphorelay proteins are essential for virulence of microbial pathogens, including the yeast fungus Candida albicans, novel antibiotics targeted to phosphorelays may be effective against eukaryotic pathogens without causing host cell damage. Unicellular organisms and cells in higher life forms have signaling pathways by which environmental stimuli are transmitted to cellular machineries that modulate metabolism and mode of growth. Signals are often propagated by the transient phosphorylation of proteins that constitute such intracellular pathways. Like many bacteria, yeast species have cellular pathways in which signaling is achieved by relaying a phosphoryl group from histidine to aspartate residues of proteins. We will discuss recent studies of the "phosphorelay" signaling systems in yeasts and their potential as targets for novel antibiotics.
Gap junctions and other mechanisms of cell–cell communication regulate basal insulin secretion in the pancreatic islet

Non‐Technical Summary The islet of Langerhans secretes the hormone insulin in response to elevated glucose. Interactions between cells within the islet is important for the regulation of insulin secretion, to both suppress basal insulin secretion and enhance the glucose‐stimulated response. We show that multiple mechanisms of cell–cell communication are required for the suppression of basal insulin release. First, gap junctions suppress spontaneous calcium signals which suppresses triggering of insulin release. Second, other juxtacrine mechanisms, regulated by cAMP and glucose, suppress more distal steps in the regulation of insulin granule exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still fully suppress basal insulin release. This new insight into the function of islet of Langerhans is important for understanding the development and treatment of diabetes.