Miracle-dz/UniFAR-FTUs huggingface dataset:
Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function

Abstract Background: Impaired glucose metabolism and cystic fibrosis (CF)-related diabetes (CFRD) are associated with insufficient weight gain and impaired lung function in children and adolescents with CF. We have asked whether imminent CFRD may be a cause of poor growth in children and adolescents. Methods: A retrospective case control study including 32 patients with CF with or without diabetes was conducted. Sixteen pairs, matched according to age, gender and exocrine pancreatic insufficiency, were analysed. Standard deviation scores (SDS) of height, growth, weight, body mass index (BMI), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and forced expiratory flow at 75% of expired FVC (FEF75) were recorded during a mean observation period of 13 years per patient. Results: SDS of height and weight were reduced in CF patients with diabetes compared to those without, not only at the point of diagnosis (both p<0.05) but years before the evidence of diabetes. Afterwards there was a significant decline in height (p<0.001) and weight (p<0.01) SDS in CFRD patients and an increasing difference between the height and weight of CF patients with or without diabetes. In contrast, no significant reduction of BMI-SDS was observed in CFRD patients. All analysed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to the diagnosis of diabetes. Conclusions: Deteriorating growth, reduced weight and impaired lung function are related to the development of CFRD and are obvious several years before the actual diagnosis of diabetes.
Postweaning, forebrain‐specific perturbation of the oxytocin system impairs fear conditioning

Oxytocin (Oxt) and vasopressin (Avp) are important for a wide variety of behaviors and the use of transgenic mice lacking the peptides or their receptors, particularly when their loss is spatially and temporally manipulated, offers an opportunity to closely examine their role in a particular behavior. We used a cued fear conditioning paradigm to examine associative learning in three lines of transgenic mice: mice that constitutively lack vasopressin 1a (Avpr1a−/−) or Oxt receptors (Oxtr−/−) and mice that have Oxt receptor loss restricted to the forebrain that begins postweaning (OxtrFB/FB). Oxtr−/− and Avpr1a−/− mice have normal conditioned freezing. OxtrFB/FB mice have a reduction in freezing behavior during acquisition, as well as during context and cue retention. In addition to reduction of Oxtr in the central nucleus of the amygdala, in vitro receptor autoradiography showed that the OxtrFB/FB mice have significantly reduced levels of Avpr1a only in that structure. Our results show that postweaning alteration of the distribution of Oxtr receptors is critically important for fear behavior, an effect mirrored in the neural structures that mediate it. While constitutive knockouts of Oxtr and Avpr1a are useful for identifying the neural underpinnings of some behaviors, compensatory mechanisms within some circuits may obscure other behavioral roles.
Ethical issues when modelling brain disorders innon-human primates

Non-human animal models of human diseases advance our knowledge of the genetic underpinnings of disease and lead to the development of novel therapies for humans. While mice are the most common model organisms, their usefulness is limited. Larger animals may provide more accurate and valuable disease models, but it has, until recently, been challenging to create large animal disease models. Genome editors, such as Clustered Randomised Interspersed Palindromic Repeat (CRISPR), meet some of these challenges and bring routine genome engineering of larger animals and non-human primates (NHPs) well within reach. There is growing interest in creating NHP models of brain disorders such as autism, depression and Alzheimer’s, which are very difficult to model or study in other organisms, including humans. New treatments are desperately needed for this set of disorders. This paper is novel in asking: Insofar as NHPs are being considered for use as model organisms for brain disorders, can this be done ethically? The paper concludes that it cannot. Notwithstanding ongoing debate about NHPs’ moral status, (1) animal welfare concerns, (2) the availability of alternative methods of studying brain disorders and (3) unmet expectations of benefit justify a stop on the creation of NHP model organisms to study brain disorders. The lure of using new genetic technologies combined with the promise of novel therapeutics presents a formidable challenge to those who call for slow, careful, and only necessary research involving NHPs. But researchers should not create macaques with social deficits or capuchin monkeys with memory deficits just because they can.
Clearing the haze: the complexities and challenges of research on state marijuana laws

As states increasingly liberalize marijuana laws, high‐quality research is needed that will inform the public and policymakers about the health and societal impact of these laws. However, there are many challenges to studying marijuana policy, including the heterogeneity of the drug and its use, the variability in the laws and their implementation from state to state, the need to capture a wide variety of relevant outcomes, and the poorly understood influence of marijuana commercialization. Furthermore, current instruments generally fail to distinguish between types of users and lack accurate and detailed measures of use. This review provides a background on marijuana laws in the United States and an overview of existing policy research, discusses methodological considerations when planning analysis of state marijuana laws, and highlights specific topics needing further development and investigation.
Maximum Entropy Low-Rank Matrix Recovery

We propose a novel, information-theoretic mask construction method, called MaxEnt, for efficient data acquisition for low-rank matrix recovery. Fundamental to this design approach is the maximum entropy principle, which states that the measurement masks which maximize the entropy of observations also maximize the information gain on the unknown matrix X. Coupled with a low-rank stochastic model for X, such a principle (i) reveals novel connections between information-theoretic sampling, compressive sensing and coding theory, and (ii) yields efficient mask construction algorithms for recovering X, which significantly outperform random measurements. We demonstrate the usefulness of MaxEnt in two real-world applications on image recovery and text document indexing1.
Well-Being: Expanding the Definition of Progress

The world is currently in the midst of unprecedented challenges—from the impacts of climate change and the humanitarian crisis of forced migration, to the rise of nationalism and epidemic growth of deaths of despair. These challenges require new approaches catalyzing communities, cities, and countries around the globe to embrace a well-being agenda to assess progress and guide solutions. Thus, this book provides ideas and guidance on advancing well-being locally, nationally, and internationally. It illuminates how diverse communities and cultures can work together to strengthen these efforts. Ultimately, the well-being framework offers an equity focus; a more human centered view of how things are going; holistic approaches; and interconnectedness. The goal here is to advance global dialogue and action on the well-being construct, and to inform the Robert Wood Johnson Foundation’s (RWJF) work with others to create a Culture of Health in the United States.
Visual Impairment in White, Chinese, Black, and Hispanic Participants from the Multi-Ethnic Study of Atherosclerosis Cohort

Abstract Purpose: To describe the prevalence of visual impairment and examine its association with demographic, socioeconomic, and health characteristics in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Methods: Visual acuity data were obtained from 6134 participants, aged 46–87 years at time of examination between 2002 and 2004 (mean age 64 years, 47.6% male), from six communities in the United States. Visual impairment was defined as presenting visual acuity 20/50 or worse in the better-seeing eye. Risk factors were included in multivariable logistic regression models to determine their impact on visual impairment for men and women in each racial/ethnic group. Results: Among all participants, 6.6% (n = 421) had visual impairment, including 5.6% of men (n = 178) and 7.5% of women (n = 243). Prevalence of impairment ranged from 4.2% (n = 52) and 6.0% (n = 77) in white men and women, respectively, to 7.6% (n = 37) and 11.6% (n = 44) in Chinese men and women, respectively. Older age was significantly associated with visual impairment in both men and women, particularly in those with lower socioeconomic status, but the effects of increasing age were more pronounced in men. Two-thirds of participants already wore distance correction, and not unexpectedly, a lower prevalence of visual impairment was seen in this group; however, 2.4% of men and 3.5% of women with current distance correction had correctable visual impairment, most notably among seniors. Conclusion: Even in the U.S. where prevalence of refractive correction is high, both visual impairment and uncorrected refractive error represent current public health challenges.
miR-216b Targets FGFR1 and Confers Sensitivity to Radiotherapy in Pancreatic Ductal Adenocarcinoma Patients Without EGFR or KRAS Mutation

Objectives The success of gemcitabine plus radiotherapy is dependent on the mutation status of pancreatic ductal adenocarcinoma (PDAC) tumors in the EGFR and KRAS genes; however, radiotherapy resistance may also be modulated epigenetically by microRNA (miRNA) regulation. In this study, we examined the potential effect of miRNAs on the resistance to radiotherapy in cases without EGFR or KRAS mutation. Methods The association of EGFR and KRAS mutation status and different expression patterns of 6 selected miRNAs related to the EGFR/KRAS signaling pathway were evaluated in the tumors of 42 patients with PDAC. Results Reduced miR-216b and miR-217 expression was associated with aggressive tumor characteristics and shortened disease-free survival. In addition, miR-216b expression was reduced 2.7-fold in the cases that did not benefit from therapy, although they did not demonstrate EGFR or KRAS expression (P = 0.0316). A negative correlation between FGFR1 and miR-216b expression (r = −0.355) was found in the tumors of these cases. Conclusions Further studies and validations are required; in the tumors of patients with PDAC without activating mutations and induced expression of EGFR/KRAS genes, down-regulated miR-216b expression may be associated with a poor response to radiotherapy via deregulation of another signaling pathway related to FGFR1 signaling.
Fantasy Proneness and Personality Profiles

This study was aimed to analyze the relationships of fantasy proneness with the personality domains encompassed within the Five-Factor Model of personality in an adult sample. A 15-item scale from the Creative Experiences Questionnaire with adequate internal consistency was used to measure fantasy proneness. The results showed two components of fantasy proneness. First one was characterized by vividness-intensity of imaginings that remained hidden for other people; the second component was composed of developmental antecedents of pretense and make-believe activities. Both components were correlated with Neuroticism (anxiety, depression, and impulsivity), Openness to Experience (fantasy, aesthetics, and feelings), and with general psychological distress and severe psychopathological symptoms. However, only the first component was associated with low Conscientiousnees (competence, order, dutifulness, and self-discipline), and only the second one was correlated with Extraversion (activity, excitement seeking, and positive emotions). Our results fitted with the notion that fantasy proneness might be a multidimensional construct.
Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk

Background: Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity. Methods: Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided. Results: In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively). Conclusions: Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3375–83)
Breast tumor cell-specific knockout of Twist1 inhibits cancer cell plasticity, dissemination, and lung metastasis in mice

Significance We found that Twist1 is coexpressed with multiple other epithelial–mesenchymal transition (EMT)-inducing transcription factors (TFs) in small subsets of primary and circulating breast tumor cells. Together, they program a partial EMT and a basal-like phenotype of tumor cells, which most likely are responsible for disseminating into the circulation and metastasizing to the lung in mice. Targeting Twist1 largely diminishes all the cellular features and phenotypes of breast tumor cells, indicating Twist1 may be a target for inhibiting breast cancer metastasis. These findings are in favor of the role of partial EMT in breast cancer progression toward the metastatic state. Twist1 is an epithelial–mesenchymal transition (EMT)-inducing transcription factor (TF) that promotes cell migration and invasion. To determine the intrinsic role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we developed mouse models with an oncogene-induced mammary tumor containing wild-type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1TKO). Twist1 knockout showed no effects on tumor initiation and growth. In both models with early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and lung metastasis was absent. Twist1 expression was detected in ∼6% of the advanced WT tumor cells. Most of these Twist1+ cells coexpressed several other EMT-inducing TFs (Snail, Slug, Zeb2), lost ERα and luminal marker K8, acquired basal cell markers (K5, p63), and exhibited a partial EMT plasticity (E-cadherin+/vimentin+). In advanced Twist1TKO tumor cells, Twist1 knockout largely diminished the expression of the aforementioned EMT-inducing TFs and basal and mesenchymal markers, but maintained the expression of the luminal markers. Circulating tumor cells (CTCs) were commonly detected in mice with advanced WT tumors, but not in mice with advanced Twist1TKO tumors. Nearly all WT CTCs coexpressed Twist1 with other EMT-inducing TFs and both epithelial and mesenchymal markers. Mice with advanced WT tumors developed extensive lung metastasis consisting of luminal tumor cells with silenced Twist1 and mesenchymal marker expression. Mice with advanced Twist1TKO tumors developed very little lung metastasis. Therefore, Twist1 is required for the expression of other EMT-inducing TFs in a small subset of tumor cells. Together, they induce partial EMT, basal-like tumor progression, intravasation, and metastasis.
A "stereo" document representation for textual information retrieval

Encouraged by a significant improvement over LSI (latent semantic indexing) approach in textual information retrieval of the DLSI (differential latent semantic indexing) approach which technically makes use of two term vectors for each document, we have proposed a concept of stereo, or multiperspective, document representation, which is expected to be effective for most of textual information retrieval approaches based on vector space model. We show that the new representation based on two or more “pictures” of each document taken from different view angles contributes to the enhanced performance of textual document retrieval by enhanced capability of extracting and capturing more individualistic features of the document. A Student t-test on experimental results on the standard Time and ADI corpora proves that the improvements of the retrieval performances of LSI/standard term vector algorithms based on multi-perspective document representation over those based on traditional single document representation are significant. ∗Corresponding Author
Detection and Genotyping of Human Papillomaviruses from Archival Formalin‐Fixed Tissue Samples

Pathology departments routinely process and store formalin‐fixed, paraffin‐embedded (FFPE) tissue samples for clinical diagnosis. These collections often contain decades’ worth of samples and represent a treasure trove of specimens that can be analyzed for retrospective epidemiological studies, diagnostics, and pathogen discovery. Accurate amplification and sequencing of DNA from these samples is critical for the usability of these FFPE samples. Here we present a collection of protocols that describe extraction of DNA from FFPE tissues, PCR amplification of human papillomavirus DNA, and subsequent genotyping of the infecting virus. © 2016 by John Wiley & Sons, Inc.
Extending Self-Esteem Theory and Research: The Science and Politics of Self-Esteem: Schools Caught in the Middle

PTA Board Member : You teach in the public schools? What subject? Teacher : Creative mathematics. When a student adds 2 & 2 and gets 7, I ask him why he came to that conclusion. If he tells me he chose the answer because it raises his self-esteem … I give him an A+. INTRODUCTION The concept of self-esteem is one of the most influential notions of our time, and certainly one of the most controversial, especially in its implications for schooling and school policy. Much has been written about the wisdom of making self-enhancement a prime goal of schools: stated in starkly contrasting terms, whether students should become good learners or feel good about themselves. Alfie Kohn (1994) comments that “by now this topic has become sufficiently polarized that the vast majority of people who address themselves to it stand in one of two camps: The pro-self-esteemers, mostly educators, who can scarcely believe that anyone would question the importance of trying to improve children's perceptions of their own worth; and the critics, who dismiss such efforts as ineffective and nonsensical distractions from academics” (p. 272). This debate is far more complex than it appears at first glance. A careful consideration of the issues reveals a nested set of interlocking claims, assumptions, and counterclaims by both sides. First comes the pro-esteem argument that fostering feelings of positive self-regard will automatically increase school achievement. Surely, these advocates argue, students who regard themselves favorably ought to be able to learn and work more effectively. Critics counter by pointing to the meager empirical support for a positive association between self-esteem, on the one hand, and school achievement on the other (see Kohn, 1994).
Callous–unemotional behaviors in early childhood: Genetic and environmental contributions to stability and change

Abstract Callous–unemotional (CU) behaviors demonstrate meaningful individual differences in early childhood, even in nonclinical samples with low mean levels of CU, but the factors underlying this variation have not been examined. This study investigated genetic and environmental contributions to individual differences and to sources of continuity and change in CU in toddler twins (145 monozygotic, 169 dizygotic) assessed at ages 2 and 3 years. CU, as assessed by the Child Behavior Checklist 1.5–5 (Achenbach & Rescorla, 2000), was moderately stable across age (r = .45, p < .0001). Longitudinal biometric analyses revealed genetic and nonshared environmental influences on CU at both ages, with no significant contribution from shared environmental factors. Stability from age 2 to 3 was due to genetic factors, whereas change was due to both genetic and nonshared environmental influences. This genetic and nonshared environmental change was substantial, suggesting malleability of CU in early childhood. Over 50% of the genetic influences and 100% of the nonshared environmental influences on CU at age 3 were independent of those that operated at age 2. Implications of novel sources of variance across age are discussed.
Src is a novel potential off‐target of RXR agonists, 9‐cis‐UAB30 and Targretin, in human breast cancer cells

9‐cis‐UAB30 (UAB30) and Targretin are well‐known retinoid X receptor (RXR) agonists. They were highly effective in decreasing the incidence of methylnitrosourea (MNU)‐induced mammary cancers. However, whether the anti‐mammary cancer effects of UAB30 or Targretin originate from the activation of RXR is unclear. In the present study, we hypothesized that UAB30 and Targretin not only affect RXR, but likely influence one or more off‐target proteins. Virtual screening results suggest that Src is a potential target for UAB30 and Targretin that regulates extracellular matrix (ECM) molecules and cell motility and invasiveness. In vitro kinase assay data revealed that UAB30 or Targretin interacted with Src and attenuated its kinase activity. We found that UAB30 or Targretin substantially inhibited invasiveness and migration of MCF‐7 and SK‐BR‐3 human breast cancer cells. We examined the effects of UAB30 and Targretin on the expression of matrix metalloproteinases (MMP)‐9, which are known to play an essential role in tumor invasion. We show that activity and expression of MMP‐9 were decreased by UAB30 or Targretin. Western blot data showed that UAB30 or Targretin decreased AKT and its substrate molecule p70s6k, which are downstream of Src in MCF‐7 and SK‐BR‐3 cells. Moreover, knocking down the expression of Src effectively reduced the sensitivity of SK‐BR‐3 cells to the inhibitory effects of UAB30 and Targretin on invasiveness. Taken together, our results demonstrate that UAB30 and Targretin each inhibit invasion and migration by targeting Src in human breast cancer cells. © 2014 Wiley Periodicals, Inc.