Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired placental trophoblast lineage differentiation in Alkbh1−/− mice

E. coli AlkB has been intensively studied since 1983, but the in vivo roles of its mammalian homologue Alkbh1 are unknown. We, therefore, created null mice for Alkbh1. Alkbh1 mRNA is expressed at highest levels in the trophoblast lineages of the developing placenta. Alkbh1−/− placentas have decreased expression of differentiated trophoblast markers including Tpbp, Gcm1, and Pl‐1, and increased expression of the trophoblast stem cell marker Eomes. Alkbh1 localizes to nuclear euchromatin, and interacts strongly with Mrj, an essential placental gene that mediates gene repression by recruitment of class II histone deacetylases (HDACs). Competition experiments show Alkbh1 and HDAC4 binding to Mrj are mutually exclusive, which causes decreased HDAC activity and increased target gene expression. Our study demonstrates Alkbh1 performs important functions in placental trophoblast lineage differentiation and participates in mechanisms of transcriptional regulation. Developmental Dynamics 237:316–327, 2008. © 2007 Wiley‐Liss, Inc.
The caregivers’ perspectives of burden before and after an internet-based intervention of young persons with ADHD or autism spectrum disorder

Abstract Background: Everyday life in a family with a young person with attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD), is multifaceted and may be a burden to the caregivers. The aim was to explore experiences of the caregiver situation, and how they were affected when the young persons received Internet-Based Support and Coaching (IBSC). Method: A multiple descriptive case design was used. Ten caregivers of 10 young persons with ADHD and/or ASD participated, and completed a questionnaire, measuring caregiver burden. Three analysis methods were used; statistical analysis of the caregivers’ scores, case reports and qualitative content analysis of an open question. Results: Most of the caregivers never had to provide hands-on help with primary ADL, and were able to cope with the young person’s problems. The caregivers’ role required patience. They had major worries about the future, when they would no longer be around to provide support. After the intervention, there was no common trajectory for all caregivers; their situation either remained unchanged, improved or deteriorated. Conclusions: The caregiver’s burden is more or less complex when the young person undergoes the transition into adulthood. The caregiver burden decreased in some families following the young person’s participation in IBSC.
Impact of an audit program and other factors on door-to-balloon times in acute ST-elevation myocardial infarction patients destined for primary coronary intervention.

OBJECTIVES This before-after study investigated the association between an audit program and door-to-balloon times in patients with acute ST-elevation myocardial infarction (STEMI) and explored other factors associated with the door-to-balloon time. METHODS An audit program that collected time data for essential time intervals in acute STEMI was developed with data feedback to both the Department of Emergency Medicine and the Department of Cardiology. The door-to-balloon times for 76 consecutive acute STEMI patients were collected from February 16, 2007, through October 31, 2007, after the implementation of the audit program, as the intervention group. The control group was defined by 104 consecutive acute STEMI patients presenting from April 1, 2006, through February 15, 2007, before the audit was applied. A multivariate linear regression model was used for analysis of factors associated with the door-to-balloon time. RESULTS The geometric mean 95% CI of the door-to-balloon time decreased from 164.9 (150.3, 180.9) minutes to 141.9 (127.4, 158.2) minutes (p = 0.039) in the intervention phase. The median door-to-balloon time was 147.5 minutes in the control group and 136.0 minutes in the intervention group (p = 0.09). In the multivariate regression model, the audit program was associated with a shortening of the door-to-balloon time by 35.5 minutes (160.4 minutes vs. 195.9 minutes, p = 0.004); female gender was associated with a mean delay of 58.4 minutes (208.9 minutes vs. 150.5 minutes; p = 0.001); posterolateral wall infarction was associated with a mean delay of 70.5 minutes compared to anterior wall infarction (215.4 minutes vs. 144.9 minutes; p = 0.037) and a mean delay of 69.5 minutes compared to inferior wall infarction (215.4 minutes vs. 145.9 minutes; p = 0.044). The use of a glycoprotein IIb/IIIa inhibitor was associated with a 46.1 minutes mean shortening of door-to-balloon time (155.7 minutes vs. 201.8 minutes; p < 0.001). CONCLUSIONS The implementation of an audit program was associated with a significant reduction in door-to-balloon times among patients with acute STEMI. In addition, female patients, posterolateral wall infarction territory, and nonuse of glycoprotein IIb/IIIa inhibitor were associated with longer door-to-balloon times.
Die Einführung von Disease-Management-Programmen in Deutschland im Spiegel unterschiedlicher Interessenlagen von Krankenkassen und Kassenärztlichen Vereinigungen

: On 1st January 2002 a law was enacted by the German Federal Government reorganising the reinsurance pool known as the "risk compensation scheme" (RSA) of the German health insurance system. This enactment contemplates a gradual restructuring of the RSA to shift from a system that considered only certain demographic criteria to one that reflects actual morbidity rates, with the shift to be phased in before full implementation by 2007. The enactment also introduced disease management programmes (DMP) for patients with certain chronic illnesses. Insurance companies will now receive additional payments from the RSA for patients with a chronic condition who are enrolled in a DMP. The intent is to improve the poor medical care for chronically ill patients in Germany - as had been stated by the advisory council of the Concerted Action in Health Care - and to reduce the natural tendency of insurance companies to prefer young healthy members over chronically ill patients. Possible consequences of the legal changes are discussed from the point of view of the various insurance companies as well as the Federal Association of Statutory Health Insurance Physicians.
Communication between integrin receptors facilitates epicardial cell adhesion and matrix organization

Formation of the epicardium requires interactions between α4β1 integrin, and the extracellular matrix. We investigated the role of other integrins expressed by epicardial cells. We detected transcripts for α5, α8, αv, β1, β3, and β5 integrins in the chick proepicardial organ (PE). We demonstrate that α5β1, α8β1, and αvβ3 integrins are expressed by chick epicardial mesothelial cells (EMCs). Migration of EMCs in vitro was reduced by RGD‐containing peptides. Using adenoviruses expressing an antisense to chick α4 (AdGFPα4AS), full‐length (Adhα4V5), and C‐terminal deleted α4 (Adhα4ΔCV5), we found that EMCs were less able to adhere to vitronectin and fibronectin120 indicating that α4β1 plays a role in regulating EMC adhesion to ligands of α5β1, α8β1, and αvβ3. In Adhα4ΔCV5‐infected EMCs, α5β1 was diminished in fibrillar adhesions and new FN matrix assembly was abnormal. We propose that cooperation between α4β1 and RGD integrins is important for EMC adhesion and subepicardial matrix formation. Developmental Dynamics 237:962–978, 2008. © 2008 Wiley‐Liss, Inc.
A single bout of resistance exercise does not modify cardiovascular responses during daily activities in patients with peripheral artery disease

ObjectiveTo analyze the posteffects of a single bout of resistance exercise on cardiovascular parameters in patients with peripheral artery disease (PAD). DesignRandomized cross-over. Materials and methodsSeventeen PAD patients performed two experimental sessions: control (C) and resistance exercise (R). Both sessions were identical (eight exercises, 3×10 repetitions), except that the R session was performed with an intensity between 5 and 7 in the OMNI-RES scale and the C session was performed without any load. Systolic blood pressure (BP), diastolic BP, heart rate, and rate–pressure product (RPP) were measured for 1 h after the interventions in the laboratory and during 24-h using ambulatory BP monitoring. ResultsAfter the R session, systolic BP (greatest reduction: −6±2 mmHg, P<0.01) and RPP (greatest reduction: −888±286 mmHg×bpm; P<0.01) decreased until 50 min after exercise. From the second hour until 23 h after exercise, BP, heart rate, and RPP product were similar (P>0.05) between R and C sessions. BP load, nocturnal BP fall, and morning surge were also similar between R and C sessions (P>0.05). ConclusionA single bout of resistance exercise decreased BP and cardiac work for 1 h after exercise under clinical conditions, and did not modify ambulatory cardiovascular variables during 24 h in patients with PAD.
Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy.
Assessment of ex-vivo and in-vivo near-infrared Raman spectroscopy for the classification of dysplasia within Barrett's esophagus

The purpose of this study is to assess if Raman spectroscopy can classify dysplastic (DYS) and early neoplastic lesions within Barrett's esophagus (BE). In BE, the normal squamous epithelium (SQ) lining the esophagus is replaced by columnar epithelium. These patients have a 30-125 fold excess risk of developing adenocarcinoma. Raman spectroscopy may provide diagnostic information so that tissue transformation may be detected at an early stage and improve the patient's prognosis. Ex vivo measurements were carried out initially on biopsy samples obtained from BE patients undergoing routine endoscopic and biopsy surveillance. Differences were noted in the spectral regions 1200-1350 cm-1 and 1550-1640 cm-1 when comparing different histopathologic grades. Principal component analysis of the spectra led to good separation between SE and BE but not between BE and DYS. Improved results were obtained using a probabilistic artificial neural network, with a resultant sensitivity and specificity of 77 percent and 93 percent in differentiating SQ/BE from dysplasia, respectively. Recently, in vivo endoscopic measurements have been performed. These preliminary results indicate that RS in combination with endoscopy may be a useful technique to screen BE patients for dysplastic/early neoplastic lesions.
Data-driven decision-making for IT capacity: beyond statistical analyses

Abstract This paper reports a research work piece developed in collaboration with the semiconductor wafer production company: STMicroelectronics. This collaborative research programme aimed at implementing statistical methods, so as to improve business decisions focusing on capacity planning for information technology. The current paper presents the specification, and experimentation of a method dedicated to managing the need to integrate rigorously complex contextualisation factors, when developing statistical-based Decision Support Systems (DSS). The key challenge is to increase the end-user acceptance and success rate for DSS developments. To ensure the successful integration of DSS within the user environment, the paper formalises a so-called ‘Contextualisation process’, integrated within a larger decision-aid development framework. This Contextualisation process is specified with three methodological components, respectively ‘Qualitative Contextualisation’, ‘Statistical Modelling and Formalisation’ and ‘User Integration’. This approach is applied by STMicroelectronics, to a case study focusing on a project of change management for the infrastructure of the Information System. Based on the demonstration of the case study results, the added-value of the Contextualisation process are discussed and further perspectives for applied research in DSS are drawn.
Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung

Fibroblast growth factor 10 (FGF10) signaling through FGF receptor 2 (FGFR2) is required for lung initiation. While studies indicate that Fgf10 and Fgfr2 are also important at later stages of lung development, their roles in early branching events remain unclear. We addressed this question through conditional inactivation of both genes in mouse subsequent to lung initiation. Inactivation of Fgf10 in lung mesenchyme resulted in smaller lobes with a reduced number of branches. Inactivation of Fgfr2 in lung epithelium resulted in disruption of lobes and small epithelial outgrowths that arose arbitrarily along the main bronchi. In both mutants, there was an increase in cell death. Also, the expression patterns of key signaling molecules implicated in branching morphogenesis were altered and a proximal lung marker was expanded distally. Our results indicate that both Fgf10 and Fgfr2 are required for a normal branching program and for proper proximal–distal patterning of the lung.Developmental Dynamics 238:1999–2013, 2009. © 2009 Wiley‐Liss, Inc.
Variable FZD7 expression in colorectal cancers indicates regulation by the tumour microenvironment

Recent evidence shows that a sub‐population of Wnt/β‐catenin target genes is specifically induced in different tissue contexts. FZD7 is a putative Wnt/β‐catenin target gene and although it is highly expressed in well‐differentiated colorectal cancer tumour cells, its expression is decreased in de‐differentiated tumour cells at the invasive front despite elevated Wnt/β‐catenin signalling in this area. This variable expression of FZD7 implicates additional regulation by the microenvironment; however, this has not been investigated. To begin to elucidate the role of extracellular matrix in regulating FZD7 expression, we generated a FZD7 promoter reporter and analysed FZD7 promoter activity in colorectal cancer cells grown on different matrices. We demonstrate that the FZD7 promoter is regulated by β‐catenin in colorectal cancer cells and observed decreased promoter activity in cells grown on fibronectin but not collagen I or collagen IV. Thus, expression of FZD7 in colorectal cancer may be regulated by fibronectin in the microenvironment. Developmental Dynamics 239:311–317, 2010. © 2009 Wiley‐Liss, Inc.
Probing the structural requirements of polybasic peptides for effective and specific amyloid reactivity

Polybasic peptides, such as peptide p5, with a predicted a-helical secondary structure bind human amyloid extracts and synthetic amyloid fibrils [1]. When radiolabeled, peptide p5 and similar reagents, such as p5 + 14 [2], have been shown to bind peripheral amyloid specifically in vivo thereby allowing imaging of the disease. At present, there are no FDA-approved clinical techniques for whole body imaging of systemic amyloidosis in patients. We hypothesize that understanding the structural features that govern amyloid binding by these small polybasic peptides will result in increased understanding of the structural requirements that are critical for specific amyloid binding. Further, this may result in the generation of enhanced
Robust marking of photoreceptor cells and pinealocytes with several reporters under control of the Crx gene

Crx is a member of the Otx family of homeobox genes with expression restricted to vertebrate retinal photoreceptor and bipolar cells as well as the pinealocytes of the pineal organ. To facilitate the visualization of Crx‐expressing cells, we generated transgenic mice expressing several reporters under the control of the Crx regulatory sequences present within a bacterial artificial chromosome (BAC). These mice expand the transgenic mouse collection, which uses photoreceptor regulatory elements for reporter gene expression by providing a broader repertoire of reporter genes. In addition, because Crx is expressed very soon after a cell fated to be a photoreceptor cell becomes postmitotic, they provide a means for early identification of immature photoreceptor cells. Developmental Dynamics 238:3218–3225, 2009. © 2009 Wiley‐Liss, Inc.
Understanding the Impact of Churn in Dynamic Oligopoly Markets

We incorporate the effects of churn, which refers to customers switching to competing brands, in a dynamic model of advertising for oligopoly markets. Each firm's market share depends not only on its own and competitors' advertising decisions, but also on market churn. Applying differential game theory, we derive a feedback Nash equilibrium under symmetric and asymmetric competition. We obtain explicit solutions and discover the counter-intuitive result that, as market churn increases, firms should decrease advertising rather than increase it to counteract the impact of churn.
Transcriptional regulatory regions of gap43 needed in developing and regenerating retinal ganglion cells

Mammals and fish differ in their ability to express axon growth‐associated genes in response to CNS injury, which contributes to the differences in their ability for CNS regeneration. Previously we demonstrated that for the axon growth‐associated gene, gap43, regions of the rat promoter that are sufficient to promote reporter gene expression in the developing zebrafish nervous system are not sufficient to promote expression in regenerating retinal ganglion cells in zebrafish. Recently, we identified a 3.6‐kb gap43 promoter fragment from the pufferfish, Takifugu rubripes (fugu), that can promote reporter gene expression during both development and regeneration. Using promoter deletion analysis, we have found regions of the 3.6‐kb fugu gap43 promoter that are necessary for expression in regenerating, but not developing, retinal ganglion cells. Within the 3.6‐kb promoter, we have identified elements that are highly conserved among fish, as well as elements conserved among fish, mammals, and birds. Developmental Dynamics 239:482–495, 2010. © 2009 Wiley‐Liss, Inc.
Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and formation of tracheal cartilage

We report that Sonic Hedgehog (Shh) regulates both formation and patterning of tracheal cartilage by controlling the expression pattern and level of the chondrogenic gene, Sox9. In Shh−/− tracheo‐esophageal tubes, Sox9 expression is transient and not restricted ventrally to the site of chondrogenesis, and is absent at the time of chondrogenesis, resulting in the failure of tracheal cartilage formation. Inhibition of Hedgehog signalling with cyclopamine in tracheal cultures prevents tracheal cartilage formation, while treatment of Shh−/− tracheal explant with exogenous Shh peptide rescues cartilage formation. Both exogenous Bmp4 and Noggin rescue cartilage phenotype in Shh−/− tracheal culture, while promoting excessive cartilage development in wild‐type trachea through induction of Sox9 expression. The ventral and segmented expression of Sox9 in tracheal primordia under Shh modulated by Bmp4 and Noggin thus determine where and when tracheal cartilage develops. These results indicate that Shh signalling is a critical determinant in tracheal cartilage development. Developmental Dynamics 239:514–526, 2010. © 2009 Wiley‐Liss, Inc.
Evaluating the use of existing data sources, probabilistic linkage, and multiple imputation to build population-based injury databases across phases of trauma care.

OBJECTIVES The objective was to evaluate the process of using existing data sources, probabilistic linkage, and multiple imputation to create large population-based injury databases matched to outcomes. METHODS This was a retrospective cohort study of injured children and adults transported by 94 emergency medical systems (EMS) agencies to 122 hospitals in seven regions of the western United States over a 36-month period (2006 to 2008). All injured patients evaluated by EMS personnel within specific geographic catchment areas were included, regardless of field disposition or outcome. The authors performed probabilistic linkage of EMS records to four hospital and postdischarge data sources (emergency department [ED] data, patient discharge data, trauma registries, and vital statistics files) and then handled missing values using multiple imputation. The authors compare and evaluate matched records, match rates (proportion of matches among eligible patients), and injury outcomes within and across sites. RESULTS There were 381,719 injured patients evaluated by EMS personnel in the seven regions. Among transported patients, match rates ranged from 14.9% to 87.5% and were directly affected by the availability of hospital data sources and proportion of missing values for key linkage variables. For vital statistics records (1-year mortality), estimated match rates ranged from 88.0% to 98.7%. Use of multiple imputation (compared to complete case analysis) reduced bias for injury outcomes, although sample size, percentage missing, type of variable, and combined-site versus single-site imputation models all affected the resulting estimates and variance. CONCLUSIONS This project demonstrates the feasibility and describes the process of constructing population-based injury databases across multiple phases of care using existing data sources and commonly available analytic methods. Attention to key linkage variables and decisions for handling missing values can be used to increase match rates between data sources, minimize bias, and preserve sampling design.
Expression patterns of sulfatase genes in the developing mouse embryo

Mammalian sulfatase enzymes participate in various processes, such as hormone regulation, lysosomal degradation and modulation of several signaling pathways. The sulfatase gene family consists of 14 members in mice and 17 in humans. Mutations of at least eight members are associated with human disorders, with main disease manifestations in the nervous system and skeleton. Despite their biological significance, little is known about their expression during embryonic development, especially for the more recently discovered gene family members. By in situ hybridization, we compared the expression patterns of nine sulfatases: ArsB, ArsG, ArsI, ArsJ, Galns, Gns, Ids, Sulf1, and Sulf2 in midgestation mouse embryos. Of interest, overlapping expression domains of several sulfatases could be detected in the developing central nervous system, eye, skeleton, and inner organs. Moreover, novel expression patterns for ArsG in choroid plexus, ArsI in hypertrophic chondrocytes and ArsJ in joints were identified. Developmental Dynamics 239:1779–1788, 2010. © 2010 Wiley‐Liss, Inc.
Assessment of in Vitro Antioxidant and Free Radical Scavenging Activity of Cajanus cajan

The present study was undertaken to evaluate the antioxidant and free radical scavenging activities of 70% methanolic extract of Cajanus cajan leaves using various in vitro assays. The TEAC value 0.84 ± 0.05 for the extract indicates it is an antioxidant. The extract had shown its scavenging activity for different free radicals and 175.73 ± 7.50 ? g/ml, 27.17 ± 0.9 ? g/ml, 60.78 ± 5.15 ? g/ml and 250.29 ± 5.70 ? g/ml were determined as the IC50 values for hydroxyl, superoxide, nitric oxide and singlet oxygen radicals, respectively. The sample showed reasonable chelation of Fe2+ ion and inhibition of lipid peroxidation. The phenolic and flavonoid contents of the extract were also determined to be 51.33 ± 0.002 mg/ml gallic acid equivalent and 143.0 ± 0.003 mg/ml quercetin equivalent, respectively. The results showed that 70% methanol extract of C. cajan leaves possesses antioxidant and free radical scavenging properties.