Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre- and postoperative studies of plasma calcitonin in primary hyperparathyroidism.

The importance of calcitonin in the homeostatic response to the chronic hypercalcemia of primary hyperparathyroidism is uncertain. To clarify this issue, we have used a new, sensitive radioimmunoassay for human calcitonin to measure basal plasma calcitonin concentrations in 50 patients with primary hyperparathyroidism (32 female, 18 male). We assayed calcium-stimulated calcitonin concentrations preoperatively in 22 of the patients (16 female, 6 male) and postoperatively in 6. Finally, we assayed pentagastrin-stimulated calcitonin concentrations preoperatively in eight of the patients (three female, five male). Plasma calcitonin values after an overnight fast were indistinguishable from those in normal subjects (mean+/-SE, males, 48+/-3 normal and 46+/-5 pg/ml hyperparathyroid, females, 31+/-2 normal and 37+/-3 pg/ml hyperparathyroid.) Among hyperparathyroid patients of both sexes, increases of calcitonin during Ca infusion (15 mg Ca/kg in 4 h) were within normal limits. However, the mean maximal increase of calcitonin was significantly lower in hyperparathyroid than in normal subjects (P < 0.05). In six patients normocalcemic 5-15 mo after parathyroid surgery, fasting plasma calcitonin values were not significantly different, but responses to Ca infusion were greater than preoperatively (Delta calcitonin +/-SE: 13+/-4 preoperatively and 53+/-35 pg/ml postoperatively). The mean maximal increase of calcitonin after pentagastrin (0.5 mug/kg i.v.) was slightly lower than normal in the patients (mean+/-SE, males, 45+/-8 normal and 38+/-10 pg/ml hyperparathyroid, females, 6+/-2 normal and 0 pg/ml hyperparathyroid). Thus, primary hyperparathyroidism is accompanied by normal steady-state concentrations of circulating calcitonin, and normal-to-blunted C-cell responses to pentagastrin or induced hypercalcemia, the response to calcium generally increasing after successful parathyroid surgery. These results clearly show that primary hyperparathyroidism is not characterized by hypercalcitoninemia. The seemingly paradoxical absence of elevated steady-state calcitonin concentrations may be accounted for partly by decreased secretory reserve. However, primary hyperparathyroidism may also be accompanied by an increase in the threshold of sensitivity for calcium stimulation of calcitonin secretion.
A Tale of Two Cities? The Heterogeneous Impact of Medicaid Managed Care

Evaluating Accountable Care Organizations is difficult because there is a great deal of heterogeneity in terms of their reimbursement incentives and other programmatic features. We examine how variation in reimbursement incentives and administration among two Medicaid managed care plans impacts utilization and spending. We use a quasi-experimental approach exploiting the timing and county-specific implementation of Medicaid managed care mandates in two contiguous regions of Kentucky. We find large differences in the relative success of each plan in reducing utilization and spending that are likely driven by important differences in plan design. The plan that capitated primary care physicians and contracted out many administrative responsibilities to an experienced managed care organization achieved significant reductions in outpatient and professional utilization. The plan that opted for a fee-for-service reimbursement scheme with a group withhold and handled administration internally saw a much more modest reduction in outpatient utilization and an increase in professional utilization.
Predictors of Technical Success and Postnatal Biventricular Outcome After In Utero Aortic Valvuloplasty for Aortic Stenosis With Evolving Hypoplastic Left Heart Syndrome

Background— Aortic stenosis in the midgestation fetus with a normal-sized or dilated left ventricle predictably progresses to hypoplastic left heart syndrome when associated with certain physiological findings. Prenatal balloon aortic valvuloplasty may improve left heart growth and function, possibly preventing evolution to hypoplastic left heart syndrome. Methods and Results— Between March 2000 and October 2008, 70 fetuses underwent attempted aortic valvuloplasty for critical aortic stenosis with evolving hypoplastic left heart syndrome. We analyzed this experience to determine factors associated with procedural and postnatal outcome. The median gestational age at intervention was 23 weeks. The procedure was technically successful in 52 fetuses (74%). Relative to 21 untreated comparison fetuses, subsequent prenatal growth of the aortic and mitral valves, but not the left ventricle, was improved after intervention. Nine pregnancies (13%) did not reach a viable term or preterm birth. Seventeen patients had a biventricular circulation postnatally, 15 from birth. Larger left heart structures and higher left ventricular pressure at the time of intervention were associated with biventricular outcome. A multivariable threshold scoring system was able to discriminate fetuses with a biventricular outcome with 100% sensitivity and modest positive predictive value. Conclusions— Technically successful aortic valvuloplasty alters left heart valvar growth in fetuses with aortic stenosis and evolving hypoplastic left heart syndrome and, in a subset of cases, appeared to contribute to a biventricular outcome after birth. Fetal aortic valvuloplasty carries a risk of fetal demise. Fetuses undergoing in utero aortic valvuloplasty with an unfavorable multivariable threshold score at the time of intervention are very unlikely to achieve a biventricular circulation postnatally.
A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa

The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs.
Empirical analysis of programming language adoption

Some programming languages become widely popular while others fail to grow beyond their niche or disappear altogether. This paper uses survey methodology to identify the factors that lead to language adoption. We analyze large datasets, including over 200,000 SourceForge projects, 590,000 projects tracked by Ohloh, and multiple surveys of 1,000-13,000 programmers. We report several prominent findings. First, language adoption follows a power law; a small number of languages account for most language use, but the programming market supports many languages with niche user bases. Second, intrinsic features have only secondary importance in adoption. Open source libraries, existing code, and experience strongly influence developers when selecting a language for a project. Language features such as performance, reliability, and simple semantics do not. Third, developers will steadily learn and forget languages. The overall number of languages developers are familiar with is independent of age. Finally, when considering intrinsic aspects of languages, developers prioritize expressivity over correctness. They perceive static types as primarily helping with the latter, hence partly explaining the popularity of dynamic languages.
Symptoms of imbalance associated with cervical spine pathology

The goals of the present study are: to determine the prevalence of dizziness or imbalance in a population of patients with cervical-spine pathology as compared to that in the general population; to determine correlations between cervical spinal pathology and symptoms of dizziness or imbalance. copyright by Catherine C. Rieke May 2009
Adaptive changes in early and late blind: a FMRI study of verb generation to heard nouns.

Literacy for blind people requires learning Braille. Along with others, we have shown that reading Braille activates visual cortex. This includes striate cortex (V1), i.e., banks of calcarine sulcus, and several higher visual areas in lingual, fusiform, cuneus, lateral occipital, inferior temporal, and middle temporal gyri. The spatial extent and magnitude of magnetic resonance (MR) signals in visual cortex is greatest for those who became blind early in life. Individuals who lost sight as adults, and subsequently learned Braille, still exhibited activity in some of the same visual cortex regions, especially V1. These findings suggest these visual cortex regions become adapted to processing tactile information and that this cross-modal neural change might support Braille literacy. Here we tested the alternative hypothesis that these regions directly respond to linguistic aspects of a task. Accordingly, language task performance by blind persons should activate the same visual cortex regions regardless of input modality. Specifically, visual cortex activity in blind people ought to arise during a language task involving heard words. Eight early blind, six late blind, and eight sighted subjects were studied using functional magnetic resonance imaging (fMRI) during covert generation of verbs to heard nouns. The control task was passive listening to indecipherable sounds (reverse words) matched to the nouns in sound intensity, duration, and spectral content. Functional responses were analyzed at the level of individual subjects using methods based on the general linear model and at the group level, using voxel based ANOVA and t-test analyses. Blind and sighted subjects showed comparable activation of language areas in left inferior frontal, dorsolateral prefrontal, and left posterior superior temporal gyri. The main distinction was bilateral, left dominant activation of the same visual cortex regions previously noted with Braille reading in all blind subjects. The spatial extent and magnitude of responses was greatest on the left in early blind individuals. Responses in the late blind group mostly were confined to V1 and nearby portions of the lingual and fusiform gyri. These results confirm the presence of adaptations in visual cortex of blind people but argue against the notion that this activity during Braille reading represents somatosensory (haptic) processing. Rather, we suggest that these responses can be most parsimoniously explained in terms of linguistic operations. It remains possible that these responses represent adaptations which initially are for processing either sound or touch, but which are later generalized to the other modality during acquisition of Braille reading skills.
Two brothers with hypospadias, hypertelorism, upper lid coloboma and mixed type hearing loss: a new syndrome

To the Editor: The first syndrome associated with hypertelorism, hypospadias and swallowing difficulty was described by Opitz et al. (1). The anomalies and related incidences reported to be associated with Opitz syndrome are as follows: ocular hypertelorism (89%), hypospadias (100? /), mild to moderate mental deficiency (38%), swallowing difficulties (69%), laryngotracheal cleft (440/0), cleft palate and bifid uvula (34%), heart defects (290/) and renal and urethral anomalies (42%) (2). We present here two patients with hypertelorism and hypospadias, but who also had upper lid coloboma and mixed type hearing loss; two different clinical features which had not previously been reported to exist in association with Opitz syndrome.
Species Richness and Altitude: A Comparison between Null Models and Interpolated Plant Species Richness along the Himalayan Altitudinal Gradient, Nepal

We compare different null models for species richness patterns in the Nepalese Himalayas, the largest altitudinal gradient in the world. Species richness is estimated by interpolation of presences between the extreme recorded altitudinal ranges. The number of species in 100‐m altitudinal bands increases steeply with altitude until 1,500 m above sea level. Between 1,500 and 2,500 m, little change in the number of species is observed, but above this altitude, a decrease in species richness is evident. We simulate different null models to investigate the effect of hard boundaries and an assumed linear relationship between species richness and altitude. We also stimulate the effect of interpolation when incomplete sampling is assumed. Some modifications on earlier simulations are presented. We demonstrate that all three factors in combination may explain the observed pattern in species richness. Estimating species richness by interpolating species presence between maximum and minimum altitudes creates an artificially steep decrease in species richness toward the ends of the gradient. The addition of hard boundaries and an underlying linear trend in species richness is needed to simulate the observed broad pattern in species richness along altitude in the Nepalese Himalayas.
Adherence to antiretroviral therapy and its determinants among persons living with HIV/AIDS in Bayelsa state, Nigeria

Background: A high level of adherence is required to achieve the desired outcomes of antiretroviral therapy. There is paucity of information about adherence to combined antiretroviral therapy in Bayelsa State of southern Nigeria. Objectives: The objectives of the study were to determine the level of adherence to combined antiretroviral therapy among the patients, evaluate the improvement in their immune status and identify reasons for sub-optimal adherence to therapy. Methods: The cross-sectional study involved administration of an adapted and pretested questionnaire to 601 consented patients attending the two tertiary health institutions in Bayesla State, Nigeria: The Federal Medical Centre, Yenagoa and the Niger-Delta University Teaching Hospital Okolobiri. The tool was divided into various sections such as socio-demographic data, HIV knowledge and adherence to combined antiretroviral therapy. Information on the patient’s CD4+ T cells count was retrieved from their medical records. Adherence was assessed by asking patients to recall their intake of prescribed doses in the last fourteen days and subjects who had 95-100% of the prescribed antiretroviral drugs were considered adherent. Results: Three hundred and forty eight (57.9%) of the subjects were females and 253 (42.1%) were males. The majority of them, 557 (92.7%) have good knowledge of HIV and combined anti-retroviral therapy with a score of 70.0% and above. A larger proportion of the respondents, 441 (73.4%), had ≥95% adherence. Some of the most important reasons giving for missing doses include, “simply forgot” 147 (24.5%), and “wanted to avoid the side-effects of drugs” 33(5.5%). There were remarkable improvements in the immune status of the subjects with an increment in the proportion of the subjects with CD4+ T cells count of greater than 350 cells/mm3 from 33 (5.5%) at therapy initiation to 338 (56.3%) at study period (p<0.0001). Conclusion: The adherence level of 73.4% was low which calls for intervention and improvement. The combined antiretroviral therapy has significantly improved the immune status of the majority of patients which must be sustained. “Simply forgot” was the most important reason for missing doses.
The Stroke Patient Who Woke Up: Clinical and Radiological Features, Including Diffusion and Perfusion MRI

Background and Purpose— Time of stroke onset is uncertain for patients who wake from sleep with stroke. Functional imaging techniques may allow estimation of benefit and risk of acute stroke therapy. We compared the clinical and multimodal MRI findings of patients with uncertain stroke onset with those with known onset time. Methods— Patients imaged within 24 hours of ischemic stroke onset between January 1997 and June 2000 were identified from a prospective stroke registry. Clinical and imaging data from patients with known stroke onset (group I) were compared with those who woke with stroke (group II). Results— A total of 364 patients were identified, of whom 100 (27%) woke from sleep with stroke. Group I and group II did not differ in age, gender, National Institutes of Health Stroke Scale, or TOAST (Trial of Org 10172 in Acute Stroke Treatment) diagnoses. Time from stroke onset was shorter in group I (mean 6.0 versus 13.3 hours, P <0.001); time from detection did not differ between groups (6.0 versus 5.9 hours). Within 3 hours, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) lesion volumes were similar in both groups; DWI-PWI mismatch was present in 82% of group I and 73% of group II patients. Mean apparent diffusion coefficient of water (ADC) of group I patients was negatively associated with DWI volume (&bgr;=−0.324, P =0.004) and time from stroke onset (&bgr;=−0.238, P =0.031) in multivariate analysis. The mean ADC of group II patients was lower than that of group I patients within 3 hours of stroke detection (mean 556 versus 665 &mgr;m2/s, P <0.01), but individual group II patients had ADC values as high as 742 &mgr;m2/s, in addition to a DWI-PWI mismatch pattern. Conclusions— Onset time is uncertain in over one quarter of acute ischemic stroke patients. Clinical features of these patients do not differ significantly from those with known onset time. Some patients who wake with stroke seem to have favorable imaging characteristics for acute stroke therapy. Further study is needed to determine whether criteria for therapy based on imaging parameters can safely be applied to these patients.
Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

Carbon nanotubes (CNTs) have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such “stealth” CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid-based nanotheranostic agents for multiplex, multimodal molecular imaging and therapy, as well as in other applications, such as drug delivery and tissue engineering.
Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox

Transforming Growth Factor-β (TGF-β) signaling in cancer has been termed the “TGF-β paradox”, acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. Here we utilize normal, weaning-induced mammary gland involution as a tissue microenvironment model to study the complexity of TGF-β function. This article reviews facets of mammary gland involution that are TGF-β regulated, namely mammary epithelial cell death, immune activation, and extracellular matrix remodeling. We outline how distinct cellular responses and crosstalk between cell types during physiologically normal mammary gland involution contribute to simultaneous tumor suppressive and promotional microenvironments. We also highlight alternatives to direct TGF-β blocking anti-cancer therapies with an emphasis on eliciting concerted microenvironmental-mediated tumor suppression.
A Classical Genetic Solution to Enhance the Biosynthesis of Anticancer Phytochemicals in Andrographis paniculata Nees

Andrographolides, the diterpene lactones, are major bioactive phytochemicals which could be found in different parts of the medicinal herb Andrographis paniculata. A number of such compounds namely andrographolide (AG), neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG) have already attracted a great deal of attention due to their potential therapeutic effects in hard-to-treat diseases such as cancers and HIV. Recently, they have also been considered as substrates for the discovery of novel pharmaceutical compounds. Nevertheless, there is still a huge gap in knowledge on the genetic pattern of the biosynthesis of these bioactive compounds. Hence, the present study aimed to investigate the genetic mechanisms controlling the biosynthesis of these phytochemicals using a diallel analysis. The high performance liquid chromatography analysis of the three andrographolides in 210 F1 progenies confirmed that the biosynthesis of these andrographolides was considerably increased via intraspecific hybridization. The results revealed high, moderate and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the preponderance of non-additive gene actions was affirmed in the enhancement of the three andrographolides contents. The consequence of this type of gene action was the occurrence of high broad-sense and low narrow-sense heritabilities for the above mentioned andrographolides. The prevalence of non-additive gene action suggests the suitability of heterosis breeding and hybrid seed production as a preferred option to produce new plant varieties with higher andrographolide contents using the wild accessions of A. paniculata. Moreover, from an evolutionary point of view, the occurrence of population bottlenecks in the Malaysian accessions of A. paniculata was unveiled by observing a low level of additive genetic variance (VA) for all the andrographolides.
Technical Note - Response Time Distribution of the M/M/m/N Queueing Model

We analyze the M/M/m/N queueing model with a first-come, first-served discipline and show that the distribution of response time (i.e., queueing time + service time) is asymptotically normal as N increases. The mean and variance of this normal distribution are both simple functions of the model parameters.