Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.
A Technique to Investigate Mural Thrombus Formation in Small Arteries and Veins: I. Comparative Morphometric and Histological Analysis

Numerous clinically relevant animal models exist for thrombosis studies. Few of these are suitable for both arteries and veins. In this investigation, an established venous thrombosis model was adapted through minimal technical adjustments to allow also the study of arterial thrombosis. A standardized subintimal crush injury was performed to carotid arteries or femoral veins of hamsters. Thrombus volumes were then quantified by direct morphometric measurements from serial microscopic sections or by on-line image analysis of light intensity changes from transilluminated vessels. The platelet-rich mural thrombus, which was established within minutes of the trauma, disintegrated during the observation period. The life cycle of the thrombus was different in arteries and veins, but significant linear correlation (p<0.01) was found in both types of vessel between thrombus volumes measured by the two techniques. The model can consequently be used for comparative in vivo thrombosis studies in small (≈1-mm) arteries and veins. Stockmans F, Stassen JM, Vermylen J, Hoylaerts MF, Nyström A. A technique to investigate mural thrombus formation in small arteries and veins: I. Comparative morphometric and histological analysis. Ann Plast Surg 1997;38:56-62
Supporting Software-Evolution at the Process Level

The ability to be changeable is inherent to software — in fact, this is what defines it as being “soft”. The long-term management of large software systems depends on the ability of a system to be “easy” to maintain and evolve. In contrast to commonly presented views, we define three ways to look at evolvability. First, it can be considered to be a quality property, and must therefore be subject to quality control. Second, it can be handled as a non-functional requirement and must therefore be part of the requirements management and change management process. Third, one could claim that it is not the system’s ability but the ability of the development and maintenance team that allows for cost-effective maintenance cycles. This in turn requires a sound understanding of the system and its environment. This paper argues that the combination of these three different views allows for a coherent understanding of maintenance and evolution of software systems. We suggest a couple of principles how to deal with long-lived systems in a systematic fashion, and derive a development process model built on
Extensive remyelination of the CNS leads to functional recovery

Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occurring simultaneously. Cats that were returned to a normal diet recovered slowly so that by 3–4 months they were neurologically normal. Histological examination of the CNS at this point showed extensive remyelination that was especially notable in the optic nerve where almost the entire nerve was remyelinated. Biochemical analysis of the diet and tissues from affected cats showed no dietary deficiencies or toxic accumulations. Thus, although the etiology of this remarkable disease remains unknown, it shows unequivocally that where axons are preserved remyelination is the default pathway in the CNS in nonimmune-mediated demyelinating disease. Most importantly, it confirms the clinical relevance of remyelination and its ability to restore function.
IL-17RA and IL-17RC Receptors Are Essential for IL-17A-Induced ELR+ CXC Chemokine Expression in Synoviocytes and Are Overexpressed in Rheumatoid Blood1

IL-17A is a cytokine secreted by the newly described Th17 cells implicated in rheumatoid arthritis (RA). Less is known about its receptors in synoviocytes. IL-17RA and IL-17RC were found to be overexpressed in RA peripheral whole blood and their expression was detected locally in RA synovium. In vitro, IL-17A synergized with TNF-α to induce IL-6, IL-8, CCL-20, and matrix metalloproteinase-3. Using microarrays, a specific up-regulation of Glu-Leu-Arg+ CXC chemokines was observed in IL-17A-treated synoviocytes. Using both posttranslational inhibitions by silencing interfering RNA and extracellular blockade by specific inhibitors, we showed that both IL-17RA and IL-17RC are implicated in IL-17A-induced IL-6 secretion, whereas in the presence of TNF-α, the inhibition of both receptors was needed to down-regulate IL-17A-induced IL-6 and CCL-20 secretion. Thus, IL-17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed in RA patients. IL-17A-induced pathogenic effects may be modulated by IL-17RA and/or IL-17RC antagonism.
Complete Resorption of Massive Soft Tissue Calcification in a Hemodialysis Patient after Parathyroidectomy

Massive soft tissue calcification involving the abdomen of a dialysis patient is described. As the result of severe secondary hyperparathyroidism associated with intensive calcifications, the patient was disabled and confined to a wheelchair. Following parathyroidectomy, soft tissue calcifications resolved remarkably, symptoms were relieved and the patient was able to walk. Our patient presented an unusual site of soft tissue calcification in secondary hyperparathyroidism and showed an example of complete resorption of soft tissue calcification after parathyroidectomy.
TP53 codon 72 polymorphisms in favorable histology Wilms tumors

In Wilms tumor (WT), mutations in the gene encoding p53, TP53, are correlated with anaplasia; however TP53 variants have not been studied in favorable histology (FH) WTs. A single nucleotide polymorphism of TP53 encoding either arginine or proline at codon 72 is suggested to alter in vitro p53 behavior. Therefore, we analyzed tissue from 23 consecutive patients with FHWT to determine allelic and genotypic frequencies of Pro72 and Arg72 variants and correlate this with clinical outcomes. Interestingly, our cohort showed a statistically significant over‐representation of the Arg allele and Arg/Arg genotype. However, the genotypic and allelic frequencies showed no significant correlation with age, stage, or disease recurrence. Pediatr Blood Cancer 2012;59:326–328. © 2011 Wiley Periodicals, Inc.
The nearly isotropic behaviour of high-rank nonlinear sequentially laminated composites

The effective transport behaviour, in the context of electrical conductivity, of sequentially laminated composites with nonlinear behaviour of the constituents is considered. An expression for the effective electric potential of two-dimensional composites is developed from the classical variational principle. This provides the means for determining the effective potential of a rank–N sequentially laminated composite with arbitrary volume fractions and lamination directions of the core laminates, in terms of an N–dimensional optimization problem. The effective potentials of sequentially laminated composites with power–law behaviour of the constituent phases are determined. It is demonstrated that the behaviour of sufficiently high–rank sequentially laminated composites tends to be isotropic. Two families of composites with both resistive and conductive inclusions are considered. The overall behaviour of these composites is compared with corresponding available bounds and estimates. It is found that the behaviours of composites belonging to these two families are, respectively, more conductive and more resistive than the corresponding second–order estimates of Ponte Castan∼eda and Kailasam.
Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France

Background: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). Objectives: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. Methods: SoJIA and AoSD patients were treated with anakinra (1–2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. Results: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3–23) and 38.1 (22–62) years, respectively; disease duration was 7.0 (1–16) and 7.8 (2–27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11–27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. Conclusion: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.
Influence of vitamin A injection before mating on oocyte development, follicular hormones, and ovulation in gilts fed high-energy diets.

Previous research revealed that treatment with vitamin A approximately 5 d before ovulation may increase litter size in weaned sows and improve embryonal survival in gilts fed high-energy diets that reduced embryonal survival. For the current study, the hypothesis was that administration of vitamin A before ovulation would alter development of follicles and oocytes in a way favorable to enhanced embryonal survival. (Landrace x Large White) x (Duroc x Hampshire) gilts (n = 44) were fed 11.0 Mcal ME x gilt(-1) x d(-1) beginning 7 d after second estrus and given (i.m.) corn oil or 1 x 10(6) IU of vitamin A (retinyl palmitate) on d 15 after second estrus. Gilts were checked for estrus every 4 h, mated naturally at third estrus, and assigned randomly to undergo midventral laparotomy beginning at 24 to 28, 28 to 32, 32 to 36, or 36 to 40 h after onset of third estrus. At laparotomy, ovulated oocytes and early-stage embryos were recovered from oviducts, and ovaries were removed for aspiration of oocytes and granulosa cells from unovulated follicles. Oocytes and embryos were stained for assessment of stage of development. Granulosa cells were cultured to assess their ability to secrete progesterone. Follicular fluid was assayed for progesterone, estradiol-17beta, IGF-I, and PGF2alpha. Treatment with vitamin A altered development of oocytes and embryos by decreasing the percentage at the germinal vesicle stage and increasing the percentage at advanced stages. Mean stage of development was increased by vitamin A, but variation in stage was decreased. Among follicles matched by meiotic stage of oocyte, follicular fluid concentrations of progesterone, IGF-I, and PGF2alpha were greater in vitamin A-treated gilts than in controls, but treatment with vitamin A in vivo did not affect LH-stimulated or unstimulated secretion of progesterone by granulosa cells in vitro. These data provide evidence that vitamin A may influence embryonic development by advancing resumption of meiosis and altering follicular hormonal environment during follicle maturation.
Falling asleep at the wheel: Motor vehicle mishaps in persons taking pramipexole and ropinirole

Article abstract The authors report a new side effect of the dopamine agonists pramipexole and ropinirole: sudden irresistible attacks of sleep. Eight PD patients taking pramipexole and one taking ropinirole fell asleep while driving, causing accidents. Five experienced no warning before falling asleep. The attacks ceased when the drugs were stopped. Neurologists who prescribe these drugs and patients who take them should be aware of this possible side effect.
A Mobile-bearing Knee Prosthesis Can Reduce Strain at the Proximal Tibia

Mobile and fixed-bearing knee prostheses are likely to generate distinct strain gradients in the proximal tibia. The resulting strain distribution in the proximal tibia governs bone remodeling and affects implant integration and stability. We determined the effects of fixed and mobile-bearing total knee prostheses on strain distribution at the proximal tibia. This mobile-bearing prosthesis was evaluated in cadaveric specimens under axial and torsional loading. Strain on the proximal tibial cortex was measured with rosette strain gages and an optical full-field strain acquisition system. Tibial torsion in response to combined axial and torsional loading was documented. There was no difference in cortex strain between the fixed and the mobile-bearing prostheses under 1.5 kN axial loading. Superimposing 10° tibial internal rotation induced 22% less compressive strain in the mobile-bearing prosthesis compared with the fixed-bearing prosthes1s. Under 10° tibial external rotation, the mobile-bearing prosthesis induced 33% less compressive strain than the fixed-bearing prosthesis. Optically acquired strain fields showed peak compressive strain at the anteromedial aspect 30 mm below the joint line. The mobile-bearing prosthesis reduced torque in the proximal tibia during knee rotation by 68-73% compared with the fixed-bearing prosthesis. Our data suggest that the particular mobile-bearing prosthesis tested potentially reduces elevated strain levels in the proximal tibia.
Effectiveness of zinc protoporphyrin/heme ratio for screening iron deficiency in preschool-aged children

Hemoglobin and zinc protoporphyrin (ZPP) tests are commonly used to screen for iron deficiency, but little research has been done to systematically evaluate the sensitivity and specificity of these two tests. The goal of this study was to evaluate the effectiveness of zinc protoporphyrin/heme (ZPP/H) ratio as a point-of-service screening test for iron deficiency among preschool-aged children by comparing the sensitivity and specificity of hemoglobin, ZPP/H ratio, and serum ferritin (SF). Also completed were assessments for the prevalence of anemia, iron deficiency (ID), and iron deficiency anemia (IDA) with indicators of ferritin models. This study was carried out with 95 children ages 3 to 6 y. Anthropometric measurements were assessed, and blood samples were analyzed for hemoglobin, SF, transferrin saturation (TS), and ZPP. Anemia was common and the prevalences of anemia, ID, and IDA were 14.7%, 12.6%, and 5.2%, respectively. The ZPP/H ratio was strongly and significantly correlated with hemoglobin. And ZPP/H ratio was a more sensitive test for ID than hemoglobin or SF measurement, correctly identifying more than twice as many iron-deficient children (sensitivity of 91.7%, compared to 41.7% for hemoglobin and SF). However, ZPP/H ratio had lower specificity (60.2%, compared to 89.1% for hemoglobin or 96.4% for SF) and resulted in the false identification of more subjects who actually were not iron deficient than did hemoglobin or SF. Low hemoglobin concentration is a late-stage indicator of ID, but ZPP/H ratio can detect ID at early stages and can be performed easily at a relatively low cost. Therefore, ZPP/H ratio can serve as a potential screening test for pre-anemic iron deficiency in community pediatric practices.
Molecular tools and bumble bees: revealing hidden details of ecology and evolution in a model system

Bumble bees are a longstanding model system for studies on behaviour, ecology and evolution, due to their well‐studied social lifestyle, invaluable role as wild and managed pollinators, and ubiquity and diversity across temperate ecosystems. Yet despite their importance, many aspects of bumble bee biology have remained enigmatic until the rise of the genetic and, more recently, genomic eras. Here, we review and synthesize new insights into the ecology, evolution and behaviour of bumble bees that have been gained using modern genetic and genomic techniques. Special emphasis is placed on four areas of bumble bee biology: the evolution of eusociality in this group, population‐level processes, large‐scale evolutionary relationships and patterns, and immunity and resistance to pesticides. We close with a prospective on the future of bumble bee genomics research, as this rapidly advancing field has the potential to further revolutionize our understanding of bumble bees, particularly in regard to adaptation and resilience. Worldwide, many bumble bee populations are in decline. As such, throughout the review, connections are drawn between new molecular insights into bumble bees and our understanding of the causal factors involved in their decline. Ongoing and potential applications to bumble bee management and conservation are also included to demonstrate how genetics‐ and genomics‐enabled research aids in the preservation of this threatened group.
Routing in Outer Space

In this paper we consider security-related and energy-efficiency issues in multi-hop wireless networks. We start our work from the observation, known in the literature, that shortest path routing creates congested areas in multi- hop wireless networks. These areas are critical-they generate both security and energy efficiency issues. We attack these problems and set out routing in outer space, a new routing mechanism that transforms any shortest path routing protocol (or an approximated version of it) into a new protocol that, in case of uniform traffic, guarantees that every node of the network is responsible for relaying the same number of messages, on expectation. We can show that a network that uses routing in outer space does not have congested areas, does not have the associated security-related issues and does not encourage selfish positioning.
Pharmacological strategies for improving diastolic dysfunction in the setting of chronic pulmonary hypertension.

BACKGROUND Right ventricular (RV) hypertrophy is an adaptive process that occurs in the setting of chronic pulmonary hypertension (CPH) and can lead to alterations in normal RV diastolic properties. This study was designed to investigate the effects of NO and milrinone on RV diastolic dysfunction in the setting of CPH and RV hypertrophy by use of a canine model of monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS Sixteen mongrel dogs (22 to 24 kg) were used. Animals underwent percutaneous pulmonary artery (PA) catheterization to measure pulmonary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after injection, all hearts were instrumented with a PA flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after both NO and milrinone administration. Diastolic properties were quantified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks after injection, significant increases in the PA pressure and pulmonary vascular resistance were observed in MCTP dogs. Significant worsening of RV diastolic function occurred in association with significant increases in the ratio of RV dry weight to LV+septal dry weight. NO and milrinone administration both led to significant improvements in RV diastolic properties. CONCLUSIONS In the setting of MCTP-induced CPH, significant worsening of RV diastolic function was observed in association with significant increases in the ratio of RV dry weight to LV+septal dry weight, suggesting that these changes are partially due to RV hypertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may be effective forms of pharmacological therapy for improving RV diastolic dysfunction in the setting of CPH.
Suppression of plasma virus load below the detection limit of a human immunodeficiency virus kit is associated with longer virologic response than suppression below the limit of quantitation.

Suppression of human immunodeficiency virus type 1 plasma virus load (PVL) to <20 copies/mL is associated with a longer virologic response after initiation of antiretroviral therapy. The relationship between duration of virologic response and PVL nadir according to a less sensitive assay was explored. When compared with subjects with a PVL nadir >500 copies/mL, the relative risks of PVL rising above 1000 copies/mL for participants in the INCAS trial and the British Columbia Drug Treatment Program with a PVL nadir below the limit of detection (LOD) were 0.04 (95% confidence interval [CI], 0.02-0.09) and 0.06 (95% CI, 0.03-0.12), respectively. The corresponding relative risks for persons with a detectable but not quantifiable PVL nadir were 0.25 (95% CI, 0.13-0.50) and 0.54 (95% CI, 0.25-1.19). The relative risks of virologic failure associated with a PVL nadir detectable but not quantifiable and a PVL nadir below the LOD were statistically different (P<.0001) in both data sets.