Miracle-dz/UniFAR-FTUs huggingface dataset:
HSD17B1 and CYP17 polymorphisms and breast cancer risk among Chinese women in Singapore

Reasons for the recent trend of increasing breast cancer incidence among Chinese and other Asian women are not well understood. Endogenous estrogen levels are strongly associated with breast cancer risk and its determinants include both genetic and lifestyle factors. We conducted a nested case‐control study to investigate, within the Singapore Chinese Health Study Cohort, the relationships between polymorphisms in 2 genes involved in estrogen metabolism, CYP17 and HSD17B1, and the risk of breast cancer. For this analysis, 188 incident breast cancer cases and 671 female cohort control subjects were compared. When the HSD17B1 A allele was considered as the “putative high‐risk” allele, there was a modest increased risk (adjusted relative risk, RR=1.37, 95% CI=0.90–2.07 for HSD17B1 AA vs. other); this association was statistically significant in analysis restricted to postmenopausal women (RR=1.86, 95% CI=1.14–3.03). There was no significant association between the CYP17 MspAI polymorphism and risk in all subjects (RR=1.06, 95% CI=0.65–1.74 for CYP17 A2A2 vs. CYP17 A1A1) or in postmenopausal women only. When we evaluated breast cancer risk in relation to the joint stratification of CYP17 and HSD17B1 genotypes and according to the combined number of putative high‐risk alleles (range, 0–4), we observed an elevated joint effect of the CYP17 and HSD17B1 genes on risk. Women who possessed all 4 putative high‐risk alleles of both genes (CYP17 A2A2 and HSD17B1 AA) vs. less displayed a nearly 2‐fold increased risk (RR=1.83, 95% CI=0.97–3.44); this finding was statistically significant in postmenopausal women (RR=2.31, 95% CI=1.07–4.98). Risk of breast cancer was similar among women possessing the other genotypes (i.e., less than 4 putative high‐risk alleles in the joint CYP17/HSD17B1 genotypes). In addition, the significant increased risk of breast cancer associated with nulliparity or late age at first live birth (age 31 years or older) was largely limited to women with the high‐risk CYP17 A1A2/A2A2 or HSD17B1 AA genotypes (RR=2.41, 95% CI=1.56–3.72; RR=4.39, 95% CI=1.71–11.30, respectively). The latter gene‐parity effects were especially pronounced in postmenopausal women. © 2003 Wiley‐Liss, Inc.
The Politics of Rulemaking in the United States

Rulemaking is a critical part of American government and governance. This article reviews the political underpinnings of modern rulemaking. Specifically, it highlights the process and impact of agency regulations, as well as the key tools used by the legislature, elected executive, and courts to oversee the rulemaking process. The article also reviews who participates in the rulemaking process, as well as who influences regulatory content. Finally, new directions in regulatory policymaking are explored, including data collection advancements, as well as the potential role for guidance documents as replacements for more traditionally issued notice and comment regulations.
Neonatal Cerebral Sinovenous Thrombosis

Neonates are known to have a higher risk of cerebral sinovenous thrombosis than children of other age groups. The exact incidence in neonates remains unknown and is likely to be underestimated, as clinical presentation is nonspecific and diagnosis can only be made when dedicated neuroimaging techniques, including computed tomographic venography or magnetic resonance venography, are performed. Associated intracranial lesions are common and some, such as a unilateral thalamic hemorrhage, should suggest cerebral sinovenous thrombosis as the underlying etiology. Neurodevelopmental outcome is poor in approximately 50% of these infants and is adversely affected by associated parenchymal lesions. Anticoagulation therapy will limit propagation of the clot and possibly the development or enhancement of parenchymal lesions. Multicenter randomized clinical trials are urgently needed to address many of these important issues.
The peptide NAP promotes neuronal growth and differentiation through extracellular signal‐regulated protein kinase and Akt pathways, and protects neurons co‐cultured with astrocytes damaged by ethanol

We have previously shown that glial cells are a target of ethanol toxicity during brain ontogeny, since ethanol affects glial development and impairs the release of neurotrophic factors which are important for neuronal outgrowth and synaptic plasticity. Activity‐dependent neuroprotective protein (ADNP) is a glial factor with anti‐apoptotic and neuroprotective actions. We proposed that some ethanol effects on brain development and synaptic formation are, in part, mediated by the ethanol‐induced impairment of the synthesis and release of ADNP by astroglial cells. We show a reduction in the ADNP mRNA levels in the cerebral cortex and astrocytes from prenatal ethanol exposed (PEE) foetuses. Furthermore, co‐cultures of PEE astrocytes with control neurons cause a marked decrease in neuronal growth, differentiation and synaptic connections relative to the co‐cultures with control astrocytes, effects that were reverted by the addition of NAP, the active peptide of ADNP. We further show that one mechanism by which NAP could exert its actions is the activation of mitogen‐activated protein kinase/extracellular signal‐regulated protein kinase, the phosphatidylinositol‐3‐kinase (PI‐3K)/Akt pathways and the transcription factor cAMP response element‐binding protein. These results indicate that the protective actions of NAP are mediated by triggering signalling pathways which are important in neuronal growth and differentiation contributing to the restoration of PEE‐associated neuronal plasticity.
Genetics of Hearing and Deafness

This article is a review of the genes and genetic disorders that affect hearing in humans and a few selected mouse models of deafness. Genetics is playing an increasingly critical role in the practice of medicine. This is not only in part to the importance that genetic knowledge has on traditional genetic diseases but also in part to the fact that genetic knowledge provides an understanding of the fundamental biological process of most diseases. The proteins coded by the genes related to hearing loss (HL) are involved in many functions in the ear, such as cochlear fluid homeostasis, ionic channels, stereocilia morphology and function, synaptic transmission, gene regulation, and others. Mouse models play a crucial role in understanding of the pathogenesis associated with these genes. Different types of familial HL have been recognized for years; however, in the last two decades, there has been tremendous progress in the discovery of gene mutations that cause deafness. Most of the cases of genetic deafness recognized today are monogenic disorders that can be broadly classified by the mode of inheritance (i.e., autosomal dominant, autosomal recessive, X‐linked, and mitochondrial inheritance) and by the presence of associated phenotypic features (i.e., syndromic; and nonsyndromic). In terms of nonsyndromic HL, the chromosomal locations are currently known for ∼ 125 loci (54 for dominant and 71 for recessive deafness), 64 genes have been identified (24 for dominant and 40 for recessive deafness), and there are many more loci for syndromic deafness and X‐linked and mitochondrial DNA disorders (http://hereditaryhearingloss.org). Thus, today's clinician must understand the science of medical genetics as this knowledge can lead to more effective disease diagnosis, counseling, treatment, and prevention. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Demineralized bone matrix and human cancellous bone enhance fixation of porous‐coated titanium implants in sheep

Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic potential and the risk of disease transmission are clinical challenges. The use of osteoinductive materials, such as demineralized bone matrix (DBM), alone or in combination with allograft or commercially available human cancellous bone (CB), may replace allografts, as they have the capability of inducing new bone and improving implant fixation through enhancing bone ongrowth. The purpose of this study was to investigate the effect of DBM alone, DBM with CB, or allograft on the fixation of porous‐coated titanium implants. DBM100 and CB produced from human tissue were included. Both materials are commercially available. DBM granules are placed in pure DBM and do not contain any other carrier. Titanium alloy implants, 10 mm long × 10 mm diameter, were inserted bilaterally into the femoral condyles of eight skeletally mature sheep. Thus, four implants with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: (a) DBM; (b) DBM:CB at a ratio of 1:3; (c) DBM:allograft at a ratio of 1:3; or (d) allograft (gold standard), respectively. A standardized surgical procedure was used. At sacrifice 6 weeks after implantation, both distal femurs were harvested. The implant fixation was evaluated by mechanical push‐out testing to test shear mechanical properties between implant and the host bone and by histomorphometry. Non‐parametric tests were applied; p < 0.05 was considered significant. Mechanical fixation showed that the strengths among the DBM/CB, DBM/allograft and allograft groups were not statistically different. The strength of the DBM group was 0.01 MPa, which was statistical significantly lower than the other three groups (p < 0.05). Histomorphometry results showed that the bone ongrowth in the DBM group was statistically significantly lower than the other three groups, while the volume fraction of new bone showed no significant difference among all the groups. Our data revealed that adding DBM to CB or to allograft resulted in comparable mechanical properties relative to the gold standard, allograft. We found inferior early effects of DBM alone on the fixation of porous‐coated titanium implant in this animal model, while the long‐term effects have to be investigated. The combination of DBM with CB, which can be used off the shelf, may represent an alternative to allograft. A cost–benefit analysis is necessary before application in clinical trial. Copyright © 2013 John Wiley & Sons, Ltd.
What can China Expect from an Increase of the Mandatory Retirement Age

Because of an aging population, China is expected to raise the mandatory retirement age in order to mitigate the pressure on its pension system. Using an Overlapping Generations model we analyze the economic impacts resulting from an increase of the life expectancy and an increased retirement age on the pension system. The results show that it is ambiguous if an increasing retirement age will cause an increase or decrease of the pension benefits. We show that, the higher the share of capital income, the more probable it becomes that an increase of retirement age will exacerbate China's pension problems.
Genetic heterogeneity within Echinococcus granulosus: isolates from different hosts and geographical areas characterized with DNA probes

SUMMARY A segment of the ribosomal RNA gene of Schistosoma mansoni and a DNA fragment specific to Echinococcus granulosus, cloned in plasmids, have been used as DNA probes to assess the extent of genetic variability within E. granulosus and some distinct strains have been identified. The DNA analysis, involving restriction endonuclease digestion and Southern blot hybridization with the probes, did not demonstrate any significant genetic variation within the U.K. horse/dog or sheep/dog strains but confirmed the distinctiveness of the two strains shown in previous studies. The sheep/dog strain was shown to be cosmopolitan in its distribution and fertile bovine material originating from the United Kingdom, Kenya, Spain and India conformed to this strain by DNA hybridization. In contrast, cattle isolates from Holland produced markedly different DNA hybridization banding profiles indicating that cattle can harbour more than one strain of E. granulosus. Similarly, it was shown that goats can harbour two different strains of E. granulosus, the sheep/dog strain and a form which infects camels. The strain of E. granulosus infecting equines in Spain and Ireland is genetically identical to that infecting horses in the United Kingdom. There is also a different strain infecting pigs in Poland and Yugoslavia. This pig/dog strain appears to be very similar genetically to the forms of E. granulosus which use camels and goats as intermediate hosts and is similar, though not identical, to the variant infecting Dutch cattle. It has been shown that E. granulosus material, fixed for a prolonged period in ethanol, or lyophilized, is amenable to DNA analysis and that it is possible to characterize the DNA of a single adult worm.
Impacts of Knowledge Management on Innovation in Higher Education Institutions: An Empirical Evidence from Vietnam

DOI: 10.14254/2071789X.2018/11-3/18 ABSTRACT. Knowledge management (KM) and innovation (INNO) are often defined as the key drivers for improvement of organizational performance. The purpose of this paper is to explore the impacts of KM on INNO in an academic environment. The results of this study are based on survey data collected during 2017 in 30 public universities equally located in 3 regions of Vietnam. Structural Equation Modelling (SEM) is used to test the hypothesized relationships between KM and INNO. The authors of this study have found that KM comprehensively impacts technical INNO in academic settings and that not all components of KM are directly associated with administrative INNO. Besides enriching the literatures on this rapport, this study is also of value in managerial perspective as it helps increase higher education institutions’ (HEIs) knowledge on how to boost their organisational innovativeness, and then enhance performance by engaging in KM activities. A list of measurement scales serving as a checklist for leadership of any HEI desire to practice KM and then boost organizational innovation is provided by this study.
Postglacial expansion and not human influence best explains the population structure in the endangered kea (Nestor notabilis)

Inferring past demography is a central question in evolutionary and conservation biology. It is, however, sometimes challenging to infer the processes that shaped the current patterns of genetic variation in endangered species. Population substructuring can occur as a result of survival in several isolated refugia and subsequent recolonization processes or via genetic drift following a population decline. The kea (Nestor notabilis) is an endemic parrot widely distributed in the mountains of the South Island of New Zealand that has gone through a major human‐induced population decline during the 1860s–1970s. The aims of this study were to understand the glacial and postglacial history of kea and to determine whether the recent population decline played a role in the shaping of the current genetic variation. We examined the distribution of genetic variation, differentiation and admixture in kea using 17 microsatellites and the mitochondrial control region. Mitochondrial data showed a shallow phylogeny and a genetic distinction between the North and South of the range consistent with the three genetic clusters identified with microsatellite data. Both marker types indicated an increase in genetic isolation by geographic distance. Approximate Bayesian Computation supported a scenario of postglacial divergence from a single ancestral glacial refugium, suggesting that the contemporary genetic structure has resulted from recolonization processes rather than from a recent population decline. The recent evolutionary origin of this genetic structure suggests that each genetic cluster does not need to be considered as independent conservation units.
The effect of accounting information quality and competition on investment inefficiency: evidence from Korea*

Abstract We examine whether either accounting quality or competition mitigates against firms’ investment inefficiency, and whether the association between accounting quality and investment inefficiency depends on the level of competition. In this paper, an analysis is undertaken of firms listed on the Korean Stock Exchange (KSE) from 2000 to 2010. The Korean economy is characterized by the ‘Chaebol’ and dominated by a creditor-oriented financing system, such that creditors have strong control over firms’ investment decisions. We believe that our own empirical results illustrate an interesting case study of the Chaebol-/bank-dominated economy, and provide additional data in this regard for academic research. Our results show that firstly, and as expected, accounting quality and competition mitigate against investment inefficiency. Managers of firms that have a higher level of accounting quality make capital investment decisions more efficiently, and their BODs monitor managers’ decision-making more effectively. For a higher level of competition in a given industry, high liquidation risks force managers to decide on capital investment more efficiently. Secondly, it is shown that accounting quality causes improvements in investment inefficiency where the level of competition in a given industry is low.
FOSL1 Controls the Assembly of Endothelial Cells into Capillary Tubes by Direct Repression of αv and β3 Integrin Transcription

ABSTRACT To form three-dimensional capillary tubes, endothelial cells must establish contacts with the extracellular matrix that provides signals for their proliferation, migration, and differentiation. The transcription factor Fosl1 plays a key role in the vasculogenic and angiogenic processes as Fosl1 knockout embryos die with vascular defects in extraembryonic tissues. Here, we show that Fosl1−/− embryonic stem cells differentiate into endothelial cells but fail to correctly assemble into primitive capillaries and to form tube-like structures. FOSL1 silencing affects in vitro angiogenesis, increases cell adhesion, and decreases cell mobility of primary human endothelial cells (HUVEC). We further show that FOSL1 is a repressor of αv and β3 integrin expression and that the down-modulation of αvβ3 rescues the angiogenic phenotype in FOSL1-silenced HUVEC, while the ectopic expression of αvβ3 alone reproduces the phenotypic alterations induced by FOSL1 knockdown. FOSL1 represses the transcription of both αv and β3 integrin genes by binding together with JunD to their proximal promoter via the transcription factor SP1. These data suggest that FOSL1-dependent negative regulation of αvβ3 expression on endothelial cells is required for endothelial assembly into vessel structures.
Temporal Genetic Dynamics of an Experimental, Biparental Field Population of Phytophthora capsici

Defining the contributions of dispersal, reproductive mode, and mating system to the population structure of a pathogenic organism is essential to estimating its evolutionary potential. After introduction of the devastating plant pathogen, Phytophthora capsici, into a grower’s field, a lack of aerial spore dispersal restricts migration. Once established, coexistence of both mating types results in formation of overwintering recombinant oospores, engendering persistent pathogen populations. To mimic these conditions, in 2008, we inoculated a field with two P. capsici isolates of opposite mating type. We analyzed pathogenic isolates collected in 2009-13 from this experimental population, using genome-wide single-nucleotide polymorphism markers. By tracking heterozygosity across years, we show that the population underwent a generational shift; transitioning from exclusively F1 in 2009-10; mixed generational in 2011; and ultimately all inbred in 2012-13. Survival of F1 oospores, characterized by heterozygosity excess, coupled with a low rate of selfing, delayed declines in heterozygosity due to inbreeding and attainment of equilibrium genotypic frequencies. Large allele and haplotype frequency changes in specific genomic regions accompanied the generational shift, representing putative signatures of selection. Finally, we identified an approximately 1.6 Mb region associated with mating type determination, constituting the first detailed genomic analysis of a mating type region (MTR) in Phytophthora. Segregation patterns in the MTR exhibited tropes of sex-linkage, where maintenance of allele frequency differences between isolates of opposite mating type was associated with elevated heterozygosity despite inbreeding. Characterizing the trajectory of this experimental system provides key insights into the processes driving persistent, sexual pathogen populations.
Strategic white matter tracts for processing speed deficits in age-related small vessel disease

Objective: Cerebral small vessel disease is the most common cause of vascular cognitive impairment and typically manifests with slowed processing speed. We investigated the impact of lesion location on processing speed in age-related small vessel disease. Methods: A total of 584 community-dwelling elderly underwent brain MRI followed by segmentation of white matter hyperintensities. Processing speed was determined by the timed measure of the Trail Making Test part B. The impact of the location of white matter hyperintensities was assessed by voxel-based lesion-symptom mapping and graph-based statistical models on regional lesion volumes in major white matter tracts. Results: Voxel-based lesion-symptom mapping identified multiple voxel clusters where the presence of white matter hyperintensities was associated with slower performance on the Trail Making Test part B. Clusters were located bilaterally in the forceps minor and anterior thalamic radiation. Region of interest–based Bayesian network analyses on lesion volumes within major white matter tracts depicted the same tracts as direct predictors for an impaired Trail Making Test part B performance. Conclusions: Our findings highlight damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in age-related small vessel disease.
Gender and Race Patterns in the Pathways from Sports Participation to Self-Esteem

Athletics is the most prominent extracurricular activity in U.S. secondary schools in terms of student participation and school budgets. The latter is often justified on the grounds that healthy bodies produce healthy minds, that school sports boost school spirit, and that participation in school-based sports increases students' self-esteem. In this article we examine the interrelationships among participation in a school-based sport and the benefits assumed to be associated with it. Specifically, we test a model that postulates that school spirit, operationalized as attachment to school, and healthy bodies, operationalized as a sense of physical well-being, mediate the relationship between school sports and self-esteem. Data from the National Longitudinal Study of Adolescent Health on Caucasian and African American girls and boys were employed to test the model. School attachment and physical well-being absorbed the statistical effect of participating in a sport for all four gender-by-race groups. Among Caucasian girls a negative residual effect of sports participation was observed, which suggests that sports participation encapsulates multiple effects with contradictory influences. For African American girls school attachment by itself was not a significant mediator of the effect of sports participation on self-esteem. For all groups a sense of physical well-being was the more powerful mediator.