Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonsyndromic hearing impairment: unparalleled heterogeneity.

Prior to 1994, only three loci for nonsyndromic hearing impairment (NSHI) had been identified. In the late 1980s, a sex-linked form of NSHI was mapped to Xql3q21.1 in Mauritian (Wallis et al. 1988) and Dutch (Brunner et al. 1988) kindreds in which affected individuals had prelingual severe to profound progressive mixed hearing impairment associated with diminished stapedial mobility and perilymphatic gushers at stapedectomy (Brunner et al. 1988). Four years later, an autosomal dominant locus was mapped to 5q31 in a large extended Costa Rican kindred that had emigrated from Jerez de la Frontera, Spain, during the early 1600s. Clinically, this type of NSHI was characterized by low-frequency hearing impairment beginning at 10 years of age and ultimately progressing to profound, irreversible, bilateral impairment, over all frequencies, by age 30 years (Leon et al. 1992). The third locus, a mitochondrial mutation, was recognized in a large Arab-Israeli pedigree with maternally inherited NSHI. An A-+G transition common both to this family and families with maternally inherited aminoglycoside-induced hearing impairment was identified in a highly conserved region of the 12S rRNA gene (nt 1555) (Prezant et al. 1993). Affected individuals had severe to profound NSHI across all frequencies, which was either congenital or rapidly progressive during early childhood (Jaber et al. 1992).
Effect‐directed analysis of sediment‐associated algal toxicants at selected hot spots in the River Elbe basin with a special focus on bioaccessibility

Benthic algae are the dominant primary producers in many rivers and may be at risk of being affected by sediment‐associated toxicants. Toxicity as well as bioaccessibility should be considered for the identification of major toxicants affecting benthic algae. Thus, effect‐directed analysis (EDA) combining biotesting, fractionation, and chemical analysis was combined with both exhaustive and bioaccessibility‐directed extraction to identify the major toxicants in sediments at three industrial sites in the Elbe River basin (Bitterfeld, Most, and Přelouč). Exhaustive accelerated solvent extraction was used together with bioaccessibility‐directed extraction with TENAX® in aqueous suspension. Growth inhibition of the green alga Scenedesmus vacuolatus identified polycyclic aromatic compounds as important algal toxicants at all three sites, while in Bitterfeld and Přelouč additional toxicants, such as N‐phenyl‐2‐naphthylamine and 7H‐benzo[de]anthracen‐7‐one, played an important role. Confirmation of the identified compounds was based on the index of confirmation quality (ICQ) comparing the effect of an artificial mixture to that of the original sample. The results suggest a successful confirmation of identified toxicants for most fractions with ICQ values between 0.5 and 2. The bioaccessibility of toxicants decreased in the order Přelouč > Bitterfeld > Most as determined by the investigation of TENAX samples. Similar total concentrations of toxicants in Přelouč and Most sediment result in bioaccessible concentrations in Přelouč that exceed those in Most by a factor of 10 to 20. The extraction with TENAX with a subsequent EDA proved to be a powerful tool for prioritizing contaminants and contaminated sites with respect to the hazard of sediment‐associated toxicants to green algae.
The Economics of Information: Markets for Seafood Attributes

This paper presents the economic theory of information, reflected by differing demand for and supply of products in the presence or absence of certain attributes. This theory is applied to the market for seafood and reviews the use of this framework in the empirical literature. Product attributes can be search attributes (demand for the product found with the lowest price or contained in preferred packaging), experience attributes (demand for a product because of previous experience with the product's taste or ease of preparation), and credence attributes (preference for products with attributes which must be identified as present by a trusted source, such as safety or recyclability). It is highly likely that, given today's competitive market for seafood and consumers' interest in knowing more about the products they purchase, the market for seafood with desired attributes will continue to evolve.
Establishment of an index with increased sensitivity for assessing murine arthritis

The goals of our study were to establish quantitative outcomes for assessing murine knee arthritis and develop an Arthritis Index that incorporates multiple outcomes into a single calculation that provides enhanced sensitivity. Using an accepted model of meniscal/ligamentous injury (MLI)‐induced osteoarthritis (OA), we assessed mouse knee arthritis using several approaches. Histology‐based methods were performed to visualize joint tissues including articular cartilage and subchondral bone. Accepted histologic scoring methods and histomorphometry were performed to grade cartilage degeneration and determine articular cartilage area, respectively. MicroCT was used to visualize and quantify the bony structures of the joint including osteophytes and joint bone volume. A statistical algorithm was then developed that combined histologic scores and cartilage areas into a single Arthritis Index. MLI induced progressive, OA‐like articular cartilage degeneration characterized by increasing (worsening) histologic score and decreasing cartilage area. MicroCT revealed osteophytes and increased joint bone volume between the femoral and tibial physes following MLI. Lastly, an Arthritis Index calculation was established, which incorporated histologic scoring and cartilage area. The Arthritis Index provided enhanced quantitative sensitivity in assessing the level of joint degeneration compared to either histologic scoring or cartilage area determination alone; when using the Index, between 29% and 43% fewer samples are needed to establish statistical significance in studies of murine arthritis. Arthritis in the mouse knee can be quantitatively assessed by histologic scoring, measuring cartilage area, and determining joint bone volume. Enhanced sensitivity can be achieved by performing the Arthritis Index calculation, a novel method for quantitatively assessing mouse knee arthritis. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1145–1151, 2011
Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells.

BACKGROUND although trastuzumab has improved the prognosis for HER-2-positive breast cancer patients, not all HER-2-positive breast tumours respond to trastuzumab treatment and those that initially respond frequently develop resistance. Insulin-like growth factor-1 receptor (IGF1R) signalling has been previously implicated in trastuzumab resistance. We tested IGF1R inhibition to determine if dual targeting of HER-2 and IGF1R improves response in cell line models of acquired trastuzumab resistance. MATERIALS AND METHODS HER-2, IGF1R, phospho-HER-2, and phospho-IGF1R levels were measured by enzyme-linked immunosorbent assays in parental and trastuzumab-resistant SKBR3 and BT474 cells. IGF1R signalling was targeted in these cells using both small interfering RNA (siRNA) and the tyrosine kinase inhibitor, NVP-AEW541. RESULTS IGF1R levels were significantly increased in the trastuzumab-resistant model, SKBR3/Tr, compared with the parental SKBR3 cell line. In both the SKBR3/Tr and BT474/Tr cell lines, inhibition of IGF1R expression with siRNA or inhibition of tyrosine kinase activity by NVP-AEW541 significantly increased response to trastuzumab. The dual targeting approach also improved response in the parental SKBR3 cells but not in the BT474 parental cells. CONCLUSIONS our results confirm that IGF1R inhibition improves response to trastuzumab in HER-2-positive breast cancer cells and suggest that dual targeting of IGF1R and HER-2 may improve response in HER-2-positive tumours.
Nifedipine and Bay K 8644 Induce an Increase of [Ca2+] i and Nitric Oxide in Endothelial Cells

Background: The dihydropyridine-induced vasorelaxation is partly dependent on the endothelium, which does not express L-type calcium channels. Because nitric oxide (NO) is one of the most important endothelium-derived vasorelaxing factors, we investigated how the calcium antagonist nifedipine and the calcium agonist Bay K 8644 modulate intracellu lar calcium and NO formation in porcine endothelial cells. Methods and Results: NO formation of porcine aortic endothelial cell cultures and of native endothelium of intact porcine coronary arteries was measured with an electrochemi cal electrode, and the intracellular concentration of Ca2+ [Ca2+]i was evaluated using the Fura-2 technique. Nifedipine induced a concentration-dependent [0.01-1 μmol/L] increase in [Ca2+]i and NO formation in cultured porcine aortic endothelial cells, and moreover a dose- dependent NO formation in native endothelial cells from intact porcine coronary arteries, which was higher than in cultured cells. This effect was inhibited by N-nitro-L-arginine, a spe cific NO synthase inhibitor. Bay K 8644 caused a [Ca2+]i increase and NO release in cul tured cells, too, although to a lesser extent. Nifedipine-induced and Bay K 8644-induced [Ca2+]i rise could be blocked by removal of extracellular calcium, indicating that a calcium influx may be involved. Conclusions: The calcium antagonist nifedipine as well as the calcium agonist Bay K 8644 cause an increase of [Ca2+]i and NO in porcine endothelium. Therefore, these effects seem to be related to the dihydropyridines as a substance class, which may explain the endothe lial component in dihydropyridine-induced vasorelaxation.
Reflections on Third World Development: Ground Level Reality, Exogenous Forces, and Conventional Paradigms

This paper argues that regional change in Third World settings is inadequately addressed by conventional development frameworks. Instead, research ought to focus on the local articulation of world economic and political conditions, donor nation actions, and policies of Third World governments. Emerging from the discussion is a research strategy that emphasizes the intersection of forces exogenous to locales and local characteristics, draws on detailed knowledge of both, and seeks to provide circumscribed generalizations. This tactic implements a fusion of approaches, blending the nomothetic perspective of development paradigms and the idiographic perspective identified with traditional regional geography.
Financial Structure and the Interest Rate Channel of the ECB Policy

This paper analyses differences in financial structure across euro area countries and their implications for the interest rate channel of the monetary transmission mechanism. It focuses on the features of financial structure that may remain different across countries in spite of EMU. First, the paper examines the pass-through of money market rates to various bank retail rates and measures how the pass-through has evolved over the last two interest-rate cycles. A panel data analysis suggests that current "country asymmetries" in the response of bank rates should decrease over time because of the implementation of the single monetary policy, money market integration and the growth of debt securities markets. It is also shown that competition among banks reduces the "interest rate cycle asymmetry" of the pass-through. Second, recent developments in the balance sheet structure of households and firms are examined. The paper shows that, at the start of EMU, the income effects of monetary policy are quite homogenous in the four biggest countries of the euro area, while, because of the importance of bond held in the portfolio of Italian households, wealth effects should be stronger in Italy.
Aprotinin Has no Effect on Platelet Activation and Adhesion during Cardiopulmonary Bypass

Summary Aprotinin reduces blood loss following cardiopulmonary bypass operations (CPB) by the prevention of hyperfibrinolysis. Its influence on circulating platelets is uncertain. In this prospective trial we investigated activation, adhesion, and aggregation receptors on the platelet surface in 20 patients who underwent elective coronary artery bypass grafting. These patients were randomly assigned to receive either a high dose of aprotinin or placebo. Flow cytometry was performed to determine platelet activation [P-selectin, glycoprotein (GP) 53], adhesive (GP Ib), and aggregatory (GP IIb-IIIa) receptors on circulating platelets, before, during, and after CPB. Aprotinin had neither a significant effect on platelet activation nor on adhesive and aggregatory receptors. Plasma levels of D-dimers were measured before and after CPB to assess fibrinolytic activity. D-dimers following CPB and chest tube drainage were significantly less in the aprotinin group. We conclude that aprotinin reduces blood loss by its effect on fibrinolysis but has no direct influence on platelet function.
Investigations into the Cause of Vertigo in Sudden Sensorineural Hearing Loss

In this light microscopic study of the temporal bone, an attempt has been made to find a morphologic correlate of vertigo associated with idiopathic sudden sensorineural hearing loss (ISSHL). Hair cell densities of the three cristae and both maculae, as well as vestibular ganglion cell (neuronal) count estimation, was done in nine ears that had documented histories of ISSHL. There were five ears with vertigo and four without. These quantitative data—i.e., hair cell densities and neuronal counts, of the vertiginous ears (group I) and nonvertiginous ears (group II)—was compared by histograms and statistically. Additionally, in each of the two groups, the data from three opposite normal hearing ears were taken as a control and used for comparison with the ISSHL ears. The differences between the vertiginous, nonvertiginous, and control ears were not significant at the 0.01 level, indicating that the vertigo was not caused by hair cell or neuronal degeneration. Gross morphologic alterations in the vestibular system, such as membrane ruptures, endolymphatic hydrops, etc., were also assessed, but no clear-cut pathology was identified in the vertiginous and nonvertiginous ears. The absence of a light microscopic morphologic correlate for vestibular disturbances associated with ISSHL suggests that the symptoms could result from ultrastructural changes in the hair cells and their synapses or from biochemical alterations in their environment.
Effect of intravitreal ranibizumab injections on aqueous humour concentrations of vascular endothelial growth factor and pigment epithelium-derived factor in patients with myopic choroidal neovascularisation

Aims To investigate aqueous humour changes in vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) levels in patients with choroidal neovascularisation (CNV) secondary to pathological myopia (mCNV) before and after intravitreal ranibizumab injection (IVR). Methods This was a prospective, case–control study investigating aqueous levels of VEGF and PEDF in eyes with mCNV treated with IVR. Results Mean VEGF and PEDF levels in the aqueous humour of control patients were 25.7±4.9 pg/mL and 12.6±3.5 ng/mL, respectively. Lower levels of both VEGF (19.5±5.4 pg/mL) and PEDF (4.7±2.2 ng/mL) were found in patients with mCNV before IVR. After IVR, aqueous VEGF levels significantly reduced to 6.5±2.7 pg/mL, while PEDF levels significantly increased to 35.8±11.4 ng/mL. VEGF and PEDF levels significantly correlated with each other, and with best-corrected visual acuity and central retinal thickness. Conclusions The VEGF and PEDF levels in aqueous humour were significantly lower in the myopic group than in controls. Moreover, IVR resulted in reduced VEGF and increased PEDF levels in patients with mCNV. In mCNV, neovascularisation is associated with inappropriate VEGF and PEDF expression. A balance between VEGF and PEDF is crucial to prevent CNV development. Trial registration number NCT02175940.
From Fuel Poverty to Energy Vulnerability: The Importance of Services, Needs and Practices.

This paper charts the emergent body of new approaches towards the research and amelioration of energy deprivation in the home. It starts from the premise that all forms of energy and fuel poverty – in developed and developing countries alike – are underpinned by a common condition: the inability to attain a socially- and materially-necessitated level of domestic energy services. Emphasizing the functionings and capabilities provided by energy use in the residential domain has led us to question binary divisions between the fields of ‘fuel poverty’ and ‘energy poverty’ within, respectively, the global North and South. In order to move towards an integrated understanding of energy service poverty, we rely on ‘systems of provision’ paradigms to highlight the multiple socio-technical pathways that prevent the effective fulfilment of household energy needs. Based on such approaches, the paper identifies the main components and implications of ‘energy vulnerability’ frameworks, whereby the driving forces of domestic energy deprivation are seen through a dynamic heuristic predicated upon issues of resilience and risk. Using recent developments in Hungary as an example, we employ energy vulnerability thinking to illustrate the systemic driving forces and implications of domestic energy deprivation.
Impacts of snow season on ground-ice accumulation, soil frost and primary productivity in a grassland of sub-Arctic Norway

Europe’s and the World’s northernmost agriculture is very vulnerable to harsh overwintering conditions. It is important from both an economic and societal standpoint to have accurate methods of predicting the severity and impact of the current snow season. Technology has advanced to enable such measurements to be regularly recorded but despite this, a detailed assessment, involving remote sensing , of the impacts of various types of snow season on agricultural yields in northernmost Europe has not previously been undertaken. Here we characterize variation in snow types and concomitant soil frost and ground-ice accumulation at a Norwegian sub-Arctic, maritime-buffered site (Tromsø, Troms County, 69 °N) during the period 1989/90 to 2013/14 and analyse how winter conditions affect agricultural productivity (both measured in the field and using remote sensing). These data were then used to build important predictive modelling approaches. In total, five contrasting types of snow season were identified, from snow-rich with no soil frost and no ground-ice to low snow and considerable soil frost and ground-ice. Conditions of low snow and low soil frost and ground-ice that result from numerous warming events were rare within the time period studied but are predicted to become the dominant snow season type. Agricultural productivity was lowest and claim settlements paid to farmers were highest after winters with high accumulation of plant-damaging, hermetic ground-ice. Deep soil frost per se did not affect primary productivity. Overall, our results together with information from other sources, suggest that icy, low snow conditions are the most challenging of all seasonal types for both the environment and livelihoods in sub-Arctic Norway. Winters with extremely deep snow also cause considerable problems. As winters are expected to warm more than summers, it is likely that the winter climate will become an even stronger regulator of northern primary productivity. To better understand the physical and biological effects of the changing winter climate, there is a requirement for continued and increasing monitoring of winter processes, especially related to frost and ice in the rhizosphere, as this is currently not well covered in national monitoring programs. Continued monitoring will enable further refinement of predictions and will support the better community planning for greatest agricultural benefit.
Twenty‐year trends in major cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Beijing

Background Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years. Methods The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010). Results Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals. Conclusions The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors.
Corruption and misconduct: A behavioural reflection from investigative reports into local government

This paper offers a local government perspective on the behavioural factors which can be the precursors for corruption and misconduct and those factors which can prevent corruption and misconduct. The investigation centred on corruption and misconduct evidenced from local government investigation reports in Australia, New Zealand and the United Kingdom. A corruption and misconduct taxonomy was developed and the role of the audit committee in the oversight of corruption and misconduct allegations in local government was empirically tested. The empirical findings indicated low support for an audit committee managing corruption and misconduct allegations. The qualitative research found that a robust culture of zero tolerance of corruption and misconduct was one of the best ways to keep a council honest.