Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Evaluation of a Genetic Risk Score for Obesity

Multi-locus profiles of genetic risk, so-called “genetic risk scores,” can be used to translate discoveries from genome-wide association studies into tools for population health research. We developed a genetic risk score for obesity from results of 16 published genome-wide association studies of obesity phenotypes in European-descent samples. We then evaluated this genetic risk score using data from the Atherosclerosis Risk in Communities (ARIC) cohort GWAS sample (N = 10,745, 55% female, 77% white, 23% African American). Our 32-locus GRS was a statistically significant predictor of body mass index (BMI) and obesity among ARIC whites [for BMI, r = 0.13, p<1 × 10−30; for obesity, area under the receiver operating characteristic curve (AUC) = 0.57 (95% CI 0.55–0.58)]. The GRS predicted differences in obesity risk net of demographic, geographic, and socioeconomic information. The GRS performed less well among African Americans. The genetic risk score we derived from GWAS provides a molecular measurement of genetic predisposition to elevated BMI and obesity. [Supplemental materials are available for this article. Go to the publisher's online edition of Biodemography and Social Biology for the following resource: Supplement to Development & Evaluation of a Genetic Risk Score for Obesity. ]
Towards sustainable water governance: Examining water governance issues in Québec through the lens of multi-loop social learning

The focus of this paper is on multi-loop social learning processes required to move towards more sustainable water governance. Multi-loop social learning is recognized as a crucial element to decision-making involving a process of managing change where the central methodological concern is with effectively engaging the necessary participation of system members in contributing to the collective knowledge for more sustainable policy outcomes. A research framework that provides a deeper understanding of the conditions required for the facilitation of multi-loop social learning is developed to assess the capacity for multi-loop social learning of the Québec water governance system. This research focuses in particular on six watershed management organizations and their watershed territories. In total, 41 semi-structured interviews were conducted with staff of the watershed management organizations as well as with actors and stakeholders associated with three of the six studied watershed territories. This study shows that although the watershed management organizations have the potential to fulfill a key role in facilitating multi-loop social learning, there are still a number of challenges that will need to be addressed to achieve this potential. Limited capacity and perceived credibility of the watershed management organizations and a mismatch between provincial- and local-level discourses, as well as a limited participation of a wide diversity of actors and stakeholders across different levels and scales, are examples of conditions that hinder the facilitation of multi-loop social learning in Québec. Opportunities to overcome some of these key challenges include renewing partnerships with stakeholders that have so far not been involved by exploring innovative tools for knowledge co-production, and accelerating the transition towards a more collaborative water governance system through the development of required traits and skills of current and future change makers and leaders.
Regulation of Mitochondrial Biogenesis by Thyroid Hormone

Thyroid hormone (T3) has a profound effect on mitochondrial biogenesis. T3‐regulated gene expression is mediated by thyroid hormone receptor (TR) binding to thyroid hormone response elements (TREs). In concert with the action of various coactivators and corepressors this interaction leads to a modulation of the chromatin structure and subsequently to a modulation of gene expression of adjacent target genes. However, as numerous genes are endogenous regulated by T3 whereas a TRE appears to be absent in their regulatory elements, a TR‐independent pathway of T3‐mediated gene regulation is likely. In this review, we discuss the direct mechanisms of TR‐dependent regulation of gene expression on the nuclear and mitochondrial genome by T3. We also summarise recent observations on an indirect mechanism of T3 action via intermediate factor(s). We discuss the regulation of nuclear respiratory factor 1 (NRF‐1) and peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC‐1α) by T3, suggesting NRF‐1 and PGC‐1α as attractive candidate factors for an intermediate factor of T3 action in vivo.
Antibiotic prescription pattern among Indian oral healthcare providers: a cross-sectional survey.

OBJECTIVES Inappropriate prescribing of antibiotics by healthcare professionals is a worldwide concern. The purpose of this study was to determine the pattern of antibiotic prescription among oral healthcare providers in India. METHODS A one-page questionnaire was sent to 1600 oral healthcare practitioners registered under the Indian Dental Association by using multistage sampling; 552 (34.5%) responded to the survey. The data were analysed using the χ(2) test and multiple logistic regression analysis. RESULTS Of 552 questionnaire respondents, 405 (73.4%) chose amoxicillin in non-allergic patients, alone [279 (50.5%)] or associated with clavulanic acid [126 (22.8%)]. The average duration of antibiotic therapy was 4.26 ± 1.26 days. The drug of first choice for patients with an allergy to penicillin was erythromycin [242 (43.8%) of respondents]. A majority prescribed antibiotics for irreversible pulpitis and acute apical periodontitis [395 (71.6%)] and necrotic pulp, acute apical periodontitis and no swelling [326 (59.1%)]. Five hundred and ten (92.4%) of the oral healthcare providers overprescribed antibiotics. CONCLUSIONS Oral healthcare providers in India are overprescribing, which could be a major contributor to the world problem of antimicrobial resistance. As there is overprescription of antibiotics by Indian oral healthcare providers, there is an urgent need to raise public and professional awareness regarding the risks of antibiotic use.
The Vibrio fischeri quorum‐sensing systems ain and lux sequentially induce luminescence gene expression and are important for persistence in the squid host

Bacterial quorum sensing using acyl‐homoserine lactones (acyl‐HSLs) as cell‐density dependent signalling molecules is important for the transcriptional regulation of many genes essential in the establishment and the maintenance of bacteria–host associations. Vibrio fischeri, the symbiotic partner of the Hawaiian bobtail squid Euprymna scolopes, possesses two distinct acyl‐HSL synthase proteins, LuxI and AinS. Whereas the cell density‐dependent regulation of luminescence by the LuxI‐produced signal is a well‐described phenomenon, and its role in light organ symbiosis has been defined, little is known about the ain system. We have investigated the impact of the V. fischeri acyl‐HSL synthase AinS on both luminescence and symbiotic colonization. Through phenotypic studies of V. fischeri mutants we have found that the AinS‐signal is the predominant inducer of luminescence expression in culture, whereas the impact of the LuxI‐signal is apparent only at the high cell densities occurring in symbiosis. Furthermore, our studies revealed that ainS regulates activities essential for successful colonization of E. scolopes, i.e. the V. fischeri ainS mutant failed to persist in the squid light organ. Mutational inactivation of the transcriptional regulator protein LuxO in the ainS mutant partially or completely reversed all the observed phenotypes, demonstrating that the AinS‐signal regulates expression of downstream genes through the inactivation of LuxO. Taken together, our results suggest that the two quorum‐sensing systems in V. fischeri, ain and lux, sequentially induce the expression of luminescence genes and possibly other colonization factors.
The 'Sharpen' filter improves the radiographic detection of vertical root fractures.

AIM To compare the diagnostic accuracy of digital enhancement filters in the diagnosis of vertical root fractures. METHODOLOGY The sample consisted of 40 single-rooted teeth randomly divided into two groups: experimental and control. Vertical root fractures were induced in the experimental group using a universal testing machine. All teeth were individually radiographed with three different horizontal angles using the Digora Optime(®) digital system. Three observers separately examined the original and filtered images (3D Emboss, Negative, Sharpen and Shadow). The area under Receiver Operating Characteristic curve values (Az) for each protocol were compared by one-way anova with post hoc Bonferroni test. The significance level was set at 5%. RESULTS The highest Az value was obtained using the Sharpen filter, with significant differences from the original and other filtered images (P < 0.05). The 3D Emboss filter had the lowest Az value, which was significantly different from the other filtered images (P < 0.05). CONCLUSION When using the Digora Optime(®) system, the 'Sharpen' filter is recommended to improve the radiographic detection of vertical root fractures.
Comparison of Amoxicillin with Alternative Agents for the Treatment of Acute Otitis Media in Children

Expert panels have recommended high‐dose amoxicillin (80–90 mg/kg/day) as the therapy of choice for uncomplicated acute otitis media in children. This recommendation is based primarily on pharmacokinetic data predicting bacteriologic cure of most middle ear infections by using amoxicillin at the recommended dosage. However, comparisons of aminopenicillin‐containing regimens with alternative treatments, particularly azithromycin, have not consistently demonstrated superiority of the former, even in recent trials with stringent designs. Moreover, amoxicillin exposure may perturb nasopharyngeal colonization more profoundly than do alternative agents. These perturbations may theoretically promote the dissemination of β‐lactam‐resistant pneumococci in the community more than other drugs approved for use in otitis media. Such findings suggest that several factors should be considered when choosing an agent to treat otitis media and that reexamination of high‐dose amoxicillin as the superior first‐line agent for this condition might be warranted.
Price Discovery between Residential Land & Housing Markets

This paper examines whether high land prices in urban areas Granger cause high property prices or whether high property prices lead to high land prices. A constant quality price index is constructed for the urban land market in Singapore using hedonic methodology. A cointegration analysis reveals that the land price and house price series are integrated in the long run and that Granger causality runs from the housing market to the land market. No reverse causality was found from the land market to the housing market. This means that price movements in the land market do not filter to the housing market in the short run.
Assessing Measurement and Predictive Invariance of the Toronto Alexithymia Scale–20 in U.S. Anglo and U.S. Hispanic Student Samples

We collected data from a predominately Anglo American student sample in the Southeastern United States and a predominately Hispanic student sample in the Southwestern United States. Along with an assessment of internal consistency reliability, we examined measurement invariance of the Toronto Alexithymia Scale–20 (TAS–20) using confirmatory factor analysis. We also assessed the predictive invariance of the TAS–20. Results indicate that 2 of the 3 TAS–20 subscales demonstrated satisfactory internal consistency reliability across samples. Items from the TAS–20 subscales demonstrated measurement invariance of the latent means. The relationship between 2 measures of emotional dysfunction and the TAS–20 also demonstrated slope and intercept invariance, indicating equivalent validity.
Estimation of repair and maintenance cost of a tractor base on HP and working hours: Case study of Sudan

A field survey was carried out in Gezira Scheme, Blue Nile State and North Kordofan State, to collect the data for tractor repair and maintenance costs, and annual hours of use of four selected models of Farmtract type tractors farmtrac80 (FT80), farmtrac70 (FT70), farmtrac60(FT60) and powertrac55 (PT55). The results showed significant (P> 0.05) differences between repair and maintenance costs in different systems of tractors. The lowest cost was recorded in the electrical system of the tractor FT 80, while the highest cost was recorded for the engine. For the tractor (PT55) the lowest cost was recorded in the hydraulic system and the highest cost was recorded in transmission system. Different mathematical regression models were also developed for accumulated repair and maintenance cost prediction such as linear, polynomial, exponential, logarithmic and power. The power model was created. The derived models indicated that the accumulated repair and maintenance costs as percentage of initial purchase price was increased as the accumulated hours of use increased for the four selected tractor models and the mean model derived.
Aspects of the geographical variations of naturally occurring 210Pb/210Po in permanent teeth of juveniles in the UK

Purpose: To study geographical variations in the level of naturally occurring 210Pb‐supported 210Po in permanent teeth of juveniles in the UK. Materials and methods: Permanent teeth extracted from 278 juveniles for orthodontic purposes were obtained from 48 counties in the UK. 210Po activity concentration was measured on the outer enamel surface using TASTRAK α‐particle‐sensitive plastic track detectors. Results: Geometric mean±SE activity concentrations in teeth from urban, suburban and rural areas, excluding the high radon area of Devon, were 8.41 +0.25/−0.24, 7.76 +0.37/−0.35 and 7.20 +0.49/−0.46 Bq kg−1, respectively. Overall, there was no significant association between α‐activity on the outer enamel surface of permanent teeth and proximity to the major UK motorways. However, when the data were considered with respect to the prevailing south‐westerly wind on the western side of the UK, a statistically significant association with respect to donors living downwind (on the easterly side) of the motorways was found. This effect was greater for sections of the M5 and M6 motorways that traverse urban areas. 210Po levels in teeth were also associated with domestic radon concentration. This effect was comparable with that from traffic and urban pollution. Conclusions: Higher levels of 210Pb‐supported 210Po are seen in permanent teeth of juveniles near sources of increased exposure in the UK. Inhalation uptake is an important pathway of exposure, especially with respect to domestic radon exposure. The results might be important in assessing integrated exposure to 210Po in the skeleton and consequent high linear energy transfer dose to bone marrow.
A review of applications of principles of quantum physics in oncology: do quantum physics principles have any role in oncology research and applications?

Abstract Background: Research in the applications of the principles of quantum physics in oncology has progressed significantly over the past decades; and several research groups with professionals from diverse scientific background, including electrical engineers, mathematicians, biologists, atomic physicists, computer programmers, and biochemists, are working collaboratively in an unprecedented and pioneering economic, organisational and human effort searching for a wider and more effective, potentially definitive, understanding of the cancers. It is hypothesised that the principles of quantum physics could open new and broader understanding of the cancers and the development of new effective, targeted, accurate, personalised and possibly definitive cancer treatment. Materials and methods: This paper reports on a review of recent studies in the field of the applications of the principles of quantum physics in biology, chemistry, biochemistry and quantum physics in cancer research, including quantum physics principles and cancer, quantum modelling techniques, quantum dots and its applications in oncology, quantum cascade laser histopathology and quantum computing applications. Conclusions: The applications of the principles of quantum physics in oncology, chemistry and biology are providing new perspectives and greater insights into a long-studied disease, which could result in a greater understanding of the cancers and the potential for personalised and definitive treatment methods.
The Case for a Pre-Cancer Genome Atlas (PCGA)

Understanding the earliest molecular and cellular events associated with cancer initiation remains a key bottleneck to transforming our approach to cancer prevention and detection. While TCGA has provided unprecedented insights into the genomic events associated with advanced stage cancer, there have been few studies comprehensively profiling premalignant and early-stage disease or elucidating the role of the microenvironment in premalignancy and tumor initiation. In this article, we make a call for development of a “Pre-Cancer Genome Atlas (PCGA),” a concerted initiative to characterize the molecular alterations in premalignant lesions and the corresponding changes in the microenvironment associated with progression to invasive carcinoma. This initiative will require a multicenter coordinated effort to comprehensively profile (cellular and molecular) premalignant lesions and their corresponding “field of injury” collected longitudinally as the lesion progresses towards or regresses from frank malignancy across multiple tumor types. Genomic characterization of alterations in premalignant lesions and their microenvironment, for both bulk tissue and single cells, will enable development of biomarkers for early detection and risk stratification as well as allow for the development of novel targeted cancer interception strategies. The multi-institutional and multidisciplinary collaborative “big-data” effort underlying the PCGA will help usher in a new era of precision medicine for cancer detection and prevention. Cancer Prev Res; 9(2); 119–24. ©2016 AACR.
Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction

Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD.
Human acetylcholine receptor presentation in myasthenia gravis. DR restriction of autoimmune T epitopes and binding of synthetic receptor sequences to DR molecules.

Autoimmune Th cells in myasthenia gravis recognize several sequence regions of the human muscle acetylcholine receptor (AChR). Most AChR Th epitopes are presented by HLA class II DR molecules (DR). Four sequence regions of the AChR alpha-subunit form Th epitopes recognized by most myasthenic patients, irrespective of their DR haplotype. In this study we first identified in five myasthenic patients the DR molecule(s) likely to be involved in presentation of T immunodominant AChR sequences. We then investigated the binding to the affinity purified DR molecules thus identified (DR2/w51, DR4/w53, and DR7/w53) and to the DR1 molecule, of a panel of overlapping synthetic peptides screening the human alpha-subunit sequence, previously used to identify AChR Th epitopes in myasthenic patients. The AChR peptides that stimulated anti-AChR autoimmune Th cells all bound the relevant DR molecules. Some AChR peptides never recognized by Th cells of myasthenic patients also bound well to one or more DR molecules. The relative ability to bind to DR molecules of different sequence regions of the AChR, i.e., an autoantigen, agrees well with the results of previous studies on the DR binding of synthetic sequences of exogenous antigens. Some peptide sequences uniquely bound one DR molecule, others bound several DR molecules, and others did not bind any of the DR molecules tested.
Molecular Determinants of Substrate Recognition in Hematopoietic Protein-tyrosine Phosphatase*

The extracellular signal-regulated protein kinase 2 (ERK2) plays a central role in cellular proliferation and differentiation. Full activation of ERK2 requires dual phosphorylation of Thr183 and Tyr185 in the activation loop. Tyr185 dephosphorylation by the hematopoietic protein-tyrosine phosphatase (HePTP) represents an important mechanism for down-regulating ERK2 activity. The bisphosphorylated ERK2 is a highly efficient substrate for HePTP with a kcat/Km of 2.6 × 106 m–1 s–1. In contrast, the kcatK/m values for the HePTP-catalyzed hydrolysis of Tyr(P) peptides are 3 orders of magnitude lower. To gain insight into the molecular basis for HePTP substrate specificity, we analyzed the effects of altering structural features unique to HePTP on the HePTP-catalyzed hydrolysis of p-nitrophenyl phosphate, Tyr(P) peptides, and its physiological substrate ERK2. Our results suggest that substrate specificity is conferred upon HePTP by both negative and positive selections. To avoid nonspecific tyrosine dephosphorylation, HePTP employs Thr106 in the substrate recognition loop as a key negative determinant to restrain its protein-tyrosine phosphatase activity. The extremely high efficiency and fidelity of ERK2 dephosphorylation by HePTP is achieved by a bipartite protein-protein interaction mechanism, in which docking interactions between the kinase interaction motif in HePTP and the common docking site in ERK2 promote the HePTP-catalyzed ERK2 dephosphorylation (∼20-fold increase in kcat/Km) by increasing the local substrate concentration, and second site interactions between the HePTP catalytic site and the ERK2 substrate-binding region enhance catalysis (∼20-fold increase in kcat/Km) by organizing the catalytic residues with respect to Tyr(P)185 for optimal phosphoryl transfer.
Decentralized control of finite state Markov processes

We are concerned with the control of a particular class of dynamic systems -- finite state Markov chains. The information pattern available is the so-called one step delay sharing information pattern. Using this information pattern, the dynamic programming algorithm can be explicitly carried out to obtain the optimal policy. The problems are discussed under three different cost criteria -- finite horizon problem with expected total cost, infinite horizon problem with discounted cost, and infinite horizon problem with average expected cost. The solution of the problem is possible with the one step delay sharing decentralized pattern because, as in the centralized control of Markov chains, a separation principle holds (this is not true for multiple step delay sharing). Hence the decentralized problem can essentially be reduced to a (more complicated) centralized one; this reduction is carried out in detail. With some modifications, the "Policy Iteration Algorithm" and "Sondik's Algorithm" are readily applied to find the optimal policies for these problems.