Miracle-dz/UniFAR-FTUs huggingface dataset:
Very Low Density Lipoprotein Receptor, a Negative Regulator of the wnt Signaling Pathway and Choroidal Neovascularization*

Choroidal neovascularization (CNV) in age-related macular degeneration is a leading cause of blindness. Very low density lipoprotein receptor gene knock-out (Vldlr-/-) mice have been shown to develop subretinal neovascularization (NV) with an unknown mechanism. The present study showed that in Vldlr-/- mice, NV initiated in the choroid and progressed to penetrate the retinal pigment epithelium layer, proliferating in the subretinal space. This phenotype recapitulated what is seen in wet age-related macular degeneration, suggesting that this is a CNV model. The CNV correlated with overexpression of vascular endothelial growth factor in Vldlr-/- eyecups and was blocked by a neutralizing antibody against vascular endothelial growth factor receptor-2. The wnt co-receptor LRP5/6 expression was significantly up-regulated in Vldlr-/- eyecups compared with that in wild-type mice. Significantly, Vldlr-/- mice showed impaired phosphorylation of downstream effectors of the wnt signaling pathway, glycogen synthase kinase-3β (GSK-3β), and β-catenin, concomitant with increased levels of free GSK-3β and β-catenin, suggesting an increased activity of the wnt pathway. Down-regulation of VLDLR by small interference RNA resulted in up-regulation of LRP5/6 expression and activation of β-catenin in cultured endothelial cells. Furthermore, Dickkopf-1, a specific inhibitor of the wnt pathway, effectively decreased vascular endothelial growth factor and β-catenin levels in the retinal pigment epithelium of Vldlr-/- mice and in cells transfected with the VLDLR small interference RNA. These results suggest that VLDLR functions as a negative regulator of CNV, and this function is mediated through the wnt pathway.
Molecular Analysis of Endometrial Hyperplasia in HNPCC-suspicious Patients May Predict Progression to Endometrial Carcinoma

Women predisposed to hereditary nonpolyposis colorectal cancer are at high risk of developing endometrial carcinoma at a young age. Hereditary nonpolyposis colorectal cancer–associated endometrial carcinomas are of the endometrioid type, usually arise from complex atypical hyperplasia, and often show microsatellite instability. To identify occult hereditary nonpolyposis colorectal cancer individuals among endometrial carcinoma patients, we examined complex atypical hyperplasias and endometrial carcinomas of 60 women ≤50 years of age (mean age: 35.7 years) using microsatellite instability, immunohistochemistry, and DNA sequence analysis. Three patient groups were recruited: group 1, patients with complex atypical hyperplasia exclusively (n = 27); group 2, patients with complex atypical hyperplasia and synchronous or metachronous endometrial carcinoma (n = 15); group 3, patients with endometrial carcinoma only (n = 18). Overall, 13 of 33 endometrial carcinomas (39%) displayed high-level microsatellite instability. None of the complex atypical hyperplasias in group 1 had high-level microsatellite instability or loss of hMLH1/hMSH2 protein expression. In group 2 patients, 33% of complex atypical hyperplasias and 53% of endometrial carcinomas had high-level microsatellite instability. Loss of hMSH2 protein expression was found in six endometrial carcinoma patients, five of them with verified hMSH2 germline mutations, including four patients with high-level microsatellite instability in complex atypical hyperplasia. Among group 3 patients, 28% of endometrial carcinomas displayed high-level microsatellite instability; three of those five endometrial carcinomas were from patients with multiple extrauterine hereditary nonpolyposis colorectal cancer–associated tumors. We conclude that young women (≤50 years of age) with concurrent complex atypical hyperplasia and multiple hereditary nonpolyposis colorectal cancer–associated carcinomas are at risk of developing high-level microsatellite instability endometrial carcinoma. Combined microsatellite instability and immunohistochemistry analysis allows the identification of a high proportion of hereditary nonpolyposis colorectal cancer patients among young women with endometrial carcinoma and complex atypical hyperplasia. All complex atypical hyperplasias with high-level microsatellite instability progressed to endometrial carcinoma. Only one third of the complex atypical hyperplasias with microsatellite stability progressed to high-level microsatellite instability endometrial carcinoma, while seven complex atypical hyperplasias progressed to microsatellite stability endometrial carcinoma. Microsatellite analysis of complex atypical hyperplasia in young patients may therefore be a useful prognostic marker for predicting possible progression to high-level microsatellite instability endometrial carcinomas.
Assessment of the Bioequivalence of Different Formulations Containing Azithromycin (Tablets and Suspension)

Summary Azithromycin (CAS 11772-70-0) is an orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. The aim of the present studies, performed in two different groups of volunteers, was to compare the bioavailability of azithromycin (Azro®) 500 mg tablets (study 1) and azithromycin (Azro®) 200 mg/5 mL suspensions (study 2) with originator products. Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in 24 healthy volunteers with a wash-out period from 14 to 21 days. Blood samples were taken up to 96 h post dosing, and concentrations of azithromycin were determined by HPLC method. In the first study, the 90 % confidence interval for intra-individual ratios (test vs. reference) of AUC0–t and Cmax of azithromycin were between 0.82 and 1.04 for AUC0–t and 0.81 and 1.11 for Cmax, and thus within the acceptance ranges for bioequivalence trials. The 90 % confidence interval for intra-individual ratios of AUC0–t and Cmax of azithromycin administered as suspension were between 0.89 and 1.22 and 0.91 and 1.23, respectively. These values were also within the acceptance range. Concerning the secondary parameter tmax the 90 % confidence interval for the intra-individual differences for azithromycin were between -0.49 - 0.50 in the first and between -0.50 - 0.25 in the second study, respectively. In the light of the results of the studies reported here it can be concluded that azithromycin test formulations, i.e. tablet and suspension are bioe-quivalent to the respective reference formulations.
The literacies of science

One starting point for a dialogue between literacy education and science education is the way in which science uses multiple literacies. Literacy education usually begins with an emphasis on language and on texts: how they're made, what they mean. Science education begins with questions about how things happen in the world. We might imagine a scientist studying literacy to be a bit like an ethnographer. An ethnographer of science and its literacies will come across other scientists making and using texts, but will look at the properties of texts only in relation to how they function in meaningful social and cultural activity.
GPSM2 and Chudley–McCullough Syndrome: A Dutch Founder Variant Brought to North America

Chudley–McCullough syndrome (CMS) is characterized by profound sensorineural hearing loss and brain anomalies. Variants in GPSM2 have recently been reported as a cause of CMS by Doherty et al. In this study we have performed exome sequencing of three CMS patients from two unrelated families from the same Dutch village. We identified one homozygous frameshift GPSM2 variants c.1473delG in all patients. We show that this variant arises from a shared, rare haplotype. Since the c.1473delG variant was found in Mennonite settlers, it likely originated in Europe. To support DNA diagnostics, we established an LOVD database for GPSM2 containing all variants thus far described. © 2013 Wiley Periodicals, Inc.
Parents’ Knowledge and Perspective of Optical Methods for Myopia Control in Children

Purpose To solicit parents’ knowledge on myopia control strategies available; to investigate their attitudes toward the use of orthokeratology (ortho-k), daily wear soft lenses, and spectacles for myopia control, assuming all three optical strategies were equally effective for myopia control; and to collect their opinion on the age at which children can commence contact lens wear for vision correction. Methods Telephone interviews were conducted on parents who responded to the advertisement for two myopia control studies, one on ortho-k and one on soft lenses. Results Most of the 196 respondents (ortho-k group, 56%; soft lens group, 44%) were mothers, aged 36 to 45 years. Ortho-k was the most commonly known myopia control strategy (86%). Parents in the ortho-k group selected ortho-k (49%) and spectacles (45%) (p < 0.001) as their preferred myopia control strategy, whereas parents in the soft lens group had no preference (p = 0.57). Decision was affected by prior knowledge of myopia control strategy. Major considerations were convenience and safety among parents selecting contact lenses and spectacles, respectively, as their preferred options. Overall, because of the lack of confidence in safety in contact lens wear, most parents (75%) were of the opinion that contact lenses for vision correction were only for children older than 14 years (53%) and not indicated for children younger than 8 years. Conclusions Parents in Hong Kong were open to the use of contact lenses for myopia control in young children and they appeared to regard myopia control contact lenses as “treatment” and not as visual aids. They were more conservative in the use of contact lenses for vision correction in children. Parents’ decision in selecting a myopia control strategy, assuming all three strategies to be equally effective, was affected by an individual’s concerns of safety and additional benefits as well as influenced by positive evidence on myopia control effects.
Incorporating the human touch: piloting a curriculum for patient-centered electronic health record use

ABSTRACT Background: Integrating electronic health records (EHRs) into clinical care can prevent physicians from focusing on patients. Despite rapid EHR adoption, few curricula teach communication skills and best practices for patient-centered EHR use. Objective: We piloted a ‘Patient-centered EHR use’ curriculum, consisting of a lecture and group-observed structured clinical examination (GOSCE) for second-year students (MS2s). Design: During the lecture, students watched a trigger tape video, engaged in a reflective observation exercise, and learned best practices. During the GOSCE, one of four MS2s interacted with a standardized patient (SP) while using the EHR. Third-year students (MS3s) received no formal training and served as a historical control group by completing the same OSCE individually. All students completed post-GOSCE/OSCE surveys. The SP evaluated GOSCE/OSCE performance. Results: In 2013, 89 MS2s participated in the workshop and GOSCEs during their required Clinical Skills course and 96 MS3s participated in individual OSCEs during their end of year multi-station formative GOSCE exercise. Eighty MS2s (90%) and 88 MS3s (92%) post-GOSCE/OSCE surveys were analyzed. Compared to MS3s, significantly more MS2s rated their knowledge (19% vs 55%) and training (14% vs 39%) as good (≥4/5 point scale, P < .001 for both). Most learners (85% MS2s and 70% MS3s) thought training should be required for all students. SP ratings on GOSCE/OSCE performance was higher for the 20 MS2s compared to the 88 MS3 controls (73.5 [SD = 4.5] vs 58.1 [SD = 13.1] on 80 point scale, P < .001). Conclusions: A short workshop and GOSCE were effective in teaching patient-centered EHR use. This curriculum is now a permanent part of our Clinical Skills course. Clerkship students who did not receive our curriculum may have been exposed to negative role-modeling on the wards. To address this, training residents and faculty on patient-centered EHR use skills should be considered. Abbreviations: EHR: Electronic health record; EHR: Electronic health record; SP: Standardized patient
IMPROVING GLYCEMIC CONTROL SAFELY IN CRITICAL CARE PATIENTS: A COLLABORATIVE SYSTEMS APPROACH IN NINE HOSPITALS.

OBJECTIVE Safely improve glycemic control in the critical care units of nine hospitals. METHODS Critical care adult inpatients from nine hospitals with ≥4 point-of-care blood glucose (BG) readings over ≥2 days were targeted by collaborative improvement efforts to reduce hyper- and hypoglycemia. Balanced glucometric goals for each hospital were set targeting improvement from baseline or goals deemed desirable from Society of Hospital Medicine (SHM) benchmarking data. Collaborative interventions included standardized insulin infusion protocols, hypoglycemia prevention bundles, audit and feedback, education, and measure-vention (coupling measurement of patients "off protocol" with concurrent interventions to correct suboptimal care). RESULTS All sites improved glycemic control. Six reached prespecified levels of improvement of the day-weighted mean BG. The day-weighted mean BG for the cohort decreased by 7.7 mg/dL (95% confidence interval [CI], 7.0 mg/dL to 8.4 mg/dL) to 151.3 mg/dL. Six of nine sites showed improvement in the percent intensive care unit (ICU) days with severe hyperglycemia (any BG >299 mg/dL). ICU severe hyperglycemic days declined from 8.6 to 7.2% for the cohort (relative risk, 0.84; 95% CI, 0.80 to 0.88). Patient days with any BG <70 mg/dL were reduced by 0.4% (95% CI, 0.06% to 0.6%), from 4.5 to 4.1%, for a small but statistically significant reduction in hypoglycemia. Seven of nine sites showed improvement. CONCLUSION Multihospital improvements in ICU glycemic control, severe hyperglycemia, and hypoglycemia are feasible. Balanced goals for glycemic control and hypoglycemia in the ICU using SHM benchmarks and metrics enhanced successful improvement efforts with good staff acceptance and sustainability. ABBREVIATIONS BG = blood glucose CMI = case-mix index CY = calendar year DKA = diabetic ketoacidosis EMR = electronic medical record GBMF = Gordon and Betty Moore Foundation ICU = intensive care unit IIP = insulin infusion protocol SHM = Society of z Hospital Medicine.
Transforming disagreements into opportunities to enhance learning, decision making and trust

Purpose – Disagreements related to processes, priorities, and purpose surface within organizations. Disagreements may be between colleagues, or between internal and external protagonists, or between managers and their direct reports. Rather than avoiding or ignoring or even trying to eradicate disagreement, this paper highlights the potential value to be extracted from disagreement and offers some ideas on how best to be in a position to do so. Design/methodology/approach – This paper is the result of the insights offered by one of the world’s leading ethicists and the reflective thought based on hundreds of discussions by all three authors with practicing managers combining for over 60 years of such engagement. Findings – Practical considerations, examples, and suggestions for extracting the benefit resident in disagreement are presented and discussed. Practical implications – The ideas and outcomes posed are immediately and broadly applicable. Originality/value – Readers are provided with an array of field-observed benefits that are potential outcomes from a conscientious engagement with disagreement. Within an organizational “climate of possibilities”, ten potential benefits from constructive engagement with disagreement are presented and discussed. In addition, ten means for enhancing the likelihood of capturing those benefits are presented.
Long‐term impacts of warming drive decomposition and accelerate the turnover of labile, not recalcitrant, carbon

Warming is altering the way soils function in ecosystems both directly by changing microbial physiology and indirectly by causing shifts in microbial community composition. Some of these warming-driven changes are short term, but others may persist over time. Here, we took advantage of a long-term (14 yr) warming experiment in a tallgrass prairie to tease apart the in ﬂ uence of short- and long-term warming on litter decomposition. We collected soils originating from warmed and control plots and incubated them with a common litter substrate in a reciprocal design under elevated and ambient growth chamber temperatures. Litter decomposition was 40% higher in soils that were warmed in the ﬁ eld for 14 yr (long-term warming) relative to soils derived from ambient plots. Short-term warming in the laboratory had less of an impact on decomposition — decomposition increased by 12% under laboratory warming. Using a two-pool soil carbon model to explore how different carbon pools may be responding, we found that long-term warming accelerated the turnover of labile, not recalcitrant, carbon in these prairie soils — a result that is likely due to shifts in soil community activity/composition. Taken together, our results offer experimental evidence that warming-induced changes in the soil community that occur over 14 yr of warming have long-lasting effects on carbon turnover.
PATIENTS' EXPERIENCES OF RECURRENT DEPRESSION

This study explores the lived experiences of individuals who are suffering from recurrent depression. Open interviews were conducted in Sweden with ten participants aged 19–67. Guided by the phenomenological method of Giorgi, data were analyzed within a Reflective Lifeworld Approach. The findings revealed a pattern of meaning, described as being alienated from oneself and others. Depression is described as an insidious disorder and participants described their experiences variously as elusive, extensive, complex, contradictory, paradoxical and stated that depression pervaded the person's whole lifeworld, involved both body and soul, and affected relationships with others. Relationships with others could be the reason for both wanting to live or to die. How best to confirm this form of suffering is something of a challenge to mental health care professionals.
Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis

Abstract Selenocysteine, the 21st genetically encoded amino acid, is the major form of the antioxidant trace element selenium in the human body. In eukaryotes and archaea its synthesis proceeds through a phosphorylated intermediate in a tRNA-dependent fashion. The final step of selenocysteine formation is catalyzed by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) that converts phosphoseryl-tRNASec to selenocysteinyl-tRNASec. The human SepSecS protein is also known as soluble liver antigen/liver pancreas (SLA/LP), which represents one of the antigens of autoimmune hepatitis. Here we review the discovery of human SepSecS and the current understanding of the immunogenicity of SLA/LP in autoimmune hepatitis.
Single-Strain versus Multistrain Inoculation: Effect of Soil Mineral N Availability on Rhizobial Strain Effectiveness and Competition for Nodulation on Chick-Pea, Soybean, and Dry Bean

The nitrogen-fixing effectiveness of multistrain inoculants was found to be determined by both the effectiveness of the component strains and the percentage of the nodules occupied by them. Multistrain formulations were always either as good as the most effective single-strain inoculant or intermediate between the most and the least effective. The percentage of nodules occupied and the amount of nitrogen fixed by the component strains of a multistrain inoculant showed highly significant linear correlation. The availability of soil N had a significant influence on the nitrogen fixation potential of each strain. The mineral N status of the soil was clearly a significant factor in affecting the competition pattern of Rhizobium loti (chick-pea) and Bradyrhizobium japonicum strains. Differences between the effectiveness of strains were masked under conditions of soil N availability. However, when soil N was immobilized with sugarcane bagasse, the differences became significant. In the chick-pea system, R. loti TAL 1148 (Nit 27A8) was the most effective but not the most competitive of the three strains used. In the soybean and dry bean systems, B. japonicum TAL 102 (USDA 110) and R. leguminosarum bv. phaseoli TAL 182, respectively, were consistently the most effective and, more often than not, the most competitive of the strains used for each species.
Influence of substratum hydration and adsorbed macromolecules on bacterial attachment to surfaces

The attachment of Pseudomonas fluorescens and an Acinetobacter sp. to hydrogel and polystyrene surfaces was investigated to evaluate the influence of adsorbed water and macromolecules on adhesion. With both organisms, there was a decrease in attachment numbers with increasing water content of the hydrogels. There was also a decrease in attachment with a decrease in water contact angle on untreated, tissue culture and sulfonated polystyrene surfaces; however, the attachment numbers were higher than would be expected on the basis of the hydrogel data. With P. fluorescens, attachment to untreated and tissue culture polystyrene was inhibited by bovine serum albumin, Escherichia coli lipopolysaccharide, and the supernatant from spent medium, both when the conditioning substances were added to the suspension of attaching cells and when they were preadsorbed onto the surfaces. Dextran inhibited attachment only when added to the bacterial suspension. Supernatants from centrifuged natural freshwater samples had no effect. Thus, hydration of a surface and the adsorption of macromolecules can reduce bacterial attachment; however, additional factors relating to the chemical composition of the substratum and polymeric stabilization of suspended cells can affect the adhesion interaction and resultant numbers of attached cells.
Demand for private healthcare in a universal public healthcare system: empirical evidence from Sri Lanka

This paper examines healthcare utilization behaviour in Sri Lanka with special emphasis on the choice between costly private and free public healthcare services. We use a data set that combines nationwide household survey data and district level healthcare supply data. Our findings suggest that even with universal public healthcare policy, richer people tend to use private sector healthcare services rather than public services. We also find significant regional and ethnic discrepancies in healthcare access bearing the risk of social tensions if these are further amplified. Latent class analysis shows in addition that the choice between private and public sector healthcare significantly differs between people with and without chronic diseases. We find in particular that chronically ill people rely for their day-to-day care on the public sector, but for their inpatient care they turn more often than non-chronically ill people to the private sector, implying an additional financial burden for the chronically ill. If the observed trend continues it may not only increase further the health-income gradient in Sri Lanka but also undermine the willingness of the middle class to pay taxes to finance public healthcare.