Miracle-dz/UniFAR-FTUs huggingface dataset:
CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity

The knirps (kni) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila. Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ‘in locus’ mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis.
Step-Based Physical Activity Metrics and Cardiometabolic Risk: NHANES 2005–2006

Purpose This study aimed to catalog the relationships between step-based accelerometer metrics indicative of physical activity volume (steps per day, adjusted to a pedometer scale), intensity (mean steps per minute from the highest, not necessarily consecutive, minutes in a day; peak 30-min cadence), and sedentary behavior (percent time at zero cadence relative to wear time; %TZC) and cardiometabolic risk factors. Methods We analyzed data from 3388 participants, 20+ yr old, in the 2005–2006 National Health and Nutrition Examination Survey with ≥1 valid day of accelerometer data and at least some data on weight, body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, HDL cholesterol, triglycerides, and/or glycohemoglobin. Linear trends were evaluated for cardiometabolic variables, adjusted for age and race, across quintiles of steps per day, peak 30-min cadence, and %TZC. Results Median steps per day ranged from 2247 to 12,334 steps per day for men and from 1755 to 9824 steps per day for women, and median peak 30-min cadence ranged from 48.1 to 96.0 steps per minute for men and from 40.8 to 96.2 steps per minute for women for the first and fifth quintiles, respectively. Linear trends were statistically significant (all P < 0.001), with increasing quintiles of steps per day and peak 30-min cadence inversely associated with waist circumference, weight, body mass index, and insulin for both men and women. Median %TZC ranged from 17.6% to 51.0% for men and from 19.9% to 47.6% for women for the first and fifth quintiles, respectively. Linear trends were statistically significant (all P < 0.05), with increasing quintiles of %TZC associated with increased waist circumference, weight and insulin for men, and insulin for women. Conclusions This analysis identified strong linear relationships between step-based movement/nonmovement dimensions and cardiometabolic risk factors. These data offer a set of quantified access points for studying the potential dose–response effects of each of these dimensions separately or collectively in longitudinal observational or intervention study designs.
Age-Related Differences in Functional Hamstring/Quadriceps Ratio Following Soccer Exercise in Female Youth Players: An Injury Risk Factor.

PURPOSE Fatigue negatively alters dynamic knee control, and the functional hamstring/quadriceps ratio (H/QFUNC) plays an important role in stabilizing the joint. The aim of this study was to investigate the influence of soccer-specific exercise on H/QFUNC in under (U) 13-, U15-, and U17-year-old female soccer players. METHODS A total of 36 female players performed concentric and eccentric actions of the hamstrings at 60°, 120°, and 180°/s before and after an age group-specific field-based soccer protocol. H/QFUNC was determined in the first 30° of knee flexion. RESULTS Significant angle × velocity (P = .001) and time × angle (P = .033) interaction effects were found indicating a lower H/QFUNC with increased movement velocity at 0°-10° as opposed to greater knee flexion angles. Fatigue-related effects were only evident near full knee extension. Probabilistic inferences indicated that changes in H/QFUNC were generally unclear in U13s, likely detrimental in U15s, and very likely beneficial in U17s. CONCLUSIONS Altered muscular control following soccer-specific exercise is age dependent with players' 1-year post-peak height velocity at greatest risk of injury. Injury prevention and screening need to be age and maturation appropriate, should consider the effects of fatigue, and include movements near full extension.
Measuring Disease Damage and Its Severity in Childhood‐Onset Systemic Lupus Erythematosus

To describe the frequency and types of disease damage occurring with childhood‐onset systemic lupus erythematosus (SLE) as measured by the 41‐item Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and to assess the SDI's ability to reflect damage severity.
First graders ' work on additive problems with the use of different notational tools

Lemke, J. (1998). Multiplying meaning: Visual and verbal semiotics in scientific text. In J.R. Martin, & R. Veel (Eds.), Reading science (pp.87-113). London: Routledge. Lemke, J. (2002). Multimedia genres for scientific education and science literacy. In M. J. Schleppegrell, & C. Colombi (Eds.), Developing advanced literacy in first and second languages (pp. 21-44). Mahwah, NJ: Lawrence Erlbaum. Mikel, G. (1996). What is scientific illustration? Retrieved from:
Perceptual Quality Assessment of Immersive Images Considering Peripheral Vision Impact

Conventional images/videos are often rendered within the central vision area of the human visual system (HVS) with uniform quality. Recent virtual reality (VR) device with head mounted display (HMD) extends the field of view (FoV) significantly to include both central and peripheral vision areas. It exhibits the unequal image quality sensation among these areas because of the non-uniform distribution of photoreceptors on our retina. We propose to study the sensation impact on the image subjective quality with respect to the eccentric angle $\theta$ across different vision areas. Often times, image quality is controlled by the quantization stepsize $q$ and spatial resolution $s$, separately and jointly. Therefore, the sensation impact can be understood by exploring the $q$ and/or $s$ in terms of the $\theta$, resulting in self-adaptive analytical models that have shown quite impressive accuracy through independent cross validations. These models can further be applied to give different quality weights at different regions, so as to significantly reduce the transmission data size but without subjective quality loss. As demonstrated in a gigapixel imaging system, we have shown that the image rendering can be speed up about 10$\times$ with the model guided unequal quality scales, in comparison to the the legacy scheme with uniform quality scales everywhere.
Labor market returns to an early childhood stimulation intervention in Jamaica

Help as hungry children helps young adults Supporters of early childhood interventions follow the rule “better early than late,” but so far there's been limited evidence that the rule applies to disadvantaged children in developing countries. Gertler et al. looked at the earnings of young adults in Jamaica, 20 years after, as toddlers, they were given 2 years of help from community health workers. The earnings of the treatment group caught up to those of a comparison group of well-fed children, but the control group of undernourished children that did not receive the health worker visits has lagged behind. Science, this issue p. 998 Encouraging greater mother-child interactions can compensate in the long term for poor nutrition. A substantial literature shows that U.S. early childhood interventions have important long-term economic benefits. However, there is little evidence on this question for developing countries. We report substantial effects on the earnings of participants in a randomized intervention conducted in 1986–1987 that gave psychosocial stimulation to growth-stunted Jamaican toddlers. The intervention consisted of weekly visits from community health workers over a 2-year period that taught parenting skills and encouraged mothers and children to interact in ways that develop cognitive and socioemotional skills. The authors reinterviewed 105 out of 129 study participants 20 years later and found that the intervention increased earnings by 25%, enough for them to catch up to the earnings of a nonstunted comparison group identified at baseline (65 out of 84 participants).
Discovery of Low Micromolar Dual Inhibitors for Wild Type and L1196M Mutant of Anaplastic Lymphoma Kinase through Structure-Based Virtual Screening

Although anaplastic lymphoma kinase (ALK) is involved in a variety of malignant human cancers, the emergence of constitutively active mutants with drug resistance has rendered it difficult to identify the new medicines for ALK-dependent cancers. To find the common inhibitors of the wild type ALK and the most abundant drug-resistant mutant (L1196M), we performed molecular docking-based virtual screening of a large chemical library in parallel for the two target proteins. As a consequence of augmenting the accuracy of the docking simulation by implementing a sophisticated hydration free energy term in the scoring function, 12 common inhibitors are discovered with the inhibitory activities ranging from submicromolar to low micromolar levels. The results of the binding free energy decomposition indicate that the biochemical potency of ALK inhibitors can be optimized by reducing the dehydration cost for binding to the receptor protein as well as by strengthening the interactions with amino acid residues in the ATP-binding site. The newly identified ALK inhibitors are found to have a little higher inhibitory activity for the L1196M mutant than for the wild type due to the strengthening of the hydrogen bond interactions in the ATP-binding site. Of the 12 common inhibitors, 2-(5-methyl-benzooxazol-2-ylamino)-quinazolin-4-ol (3) is anticipated to serve as a new molecular scaffold to optimize the biochemical potency because it exhibits low micromolar inhibitory activity with respect to both the wild type and L1196M mutant in spite of the low molecular weight (292.3 amu).
The potential of microRNAs as human prostate cancer biomarkers: A meta‐analysis of related studies

Prostate cancer (PC) is a very important kind of male malignancies. When PC evolves into a stage of hormone resistance or metastasis, the fatality rate is very high. Currently, discoveries and advances in miRNAs as biomarkers have opened the potential for the diagnosis of PC, especially early diagnosis. miRNAs not only can noninvasively or minimally invasively identify PC, but also can provide the data for optimization and personalization of therapy. Moreover, miRNAs have been shown to play an important role to predict prognosis of PC. The purpose of this meta‐analysis is to integrate the currently published expression profile data of miRNAs in PC, and evaluate the value of miRNAs as biomarkers for PC. All of relevant records were selected via electronic databases: Pubmed, Embase, Cochrane, and CNKI based on the assessment of title, abstract, and full text. we extracted mean ± SD or fold change of miRNAs expression levels in PC versus BPH or normal controls. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and recurrence‐free survival (RFS), were also calculated to detect the relationship between high miRNAs expression and PC prognosis. Selected 104 articles were published in 2007‐2017. According to the inclusion criteria, 104 records were included for this meta‐analysis. The pooled or stratified analyze showed 10 up‐regulated miRNAs (miR‐18a, miR‐34a, miR‐106b, miR‐141, miR‐182, miR‐183, miR‐200a/b, miR‐301a, and miR‐375) and 14 down‐regulated miRNAs (miR‐1, miR‐23b/27b, miR‐30c, miR‐99b, miR‐139‐5p, miR‐152, miR‐187, miR‐204, miR‐205, miR‐224, miR‐452, miR‐505, and let‐7c) had relatively good diagnostic and predictive potential to discriminate PC from BPH/normal controls. Furthermore, high expression of miR‐32 and low expression of let‐7c could be used to differentiate metastatic PC from local/primary PC. Additional interesting findings were that the expression profiles of five miRNAs (miR‐21, miR‐30c, miR‐129, miR‐145, and let‐7c) could predict poor RFS of PC, while the evaluation of miR‐375 was associated with worse OS. miRNAs are important regulators in PC progression. Our results indicate that miRNAs are suitable for predicting the different stages of PC. The detection of miRNAs is an effective way to control patient's prognosis and evaluate therapeutic efficacy. However, large‐scale detections based on common clinical guidelines are still necessary to further validate our conclusions, due to the bias induced by molecular heterogeneity and differences in study design and detection methods.
Dental Trauma: Knowledge and Attitudes of Community Health Workers

Background The international literature emphasizes the importance of evaluating the knowledge of different groups such as teachers, students, dentists, physicians, parents, and athletes regarding dental injuries. In Brazil, community health workers are professionals who can reach a wide variety of people and who have a marked influence on prevention and health promotion strategies. The objective of this study was to investigate the knowledge and attitudes of community health workers regarding dental trauma. Methods A questionnaire consisting of 19 questions divided into 3 parts was applied: demographic characteristics, knowledge, and attitudes. Data from 206 respondents were analyzed using descriptive statistics and logistic regression models. Results Approximately 28% of the participants reported to have been called to assist individuals with dental trauma. Only 42 subjects had received education on dental injuries, with 34 of them being instructed by a dentist. In cases of tooth avulsion, only 1.9% of the health workers reported that they would search for the tooth and reimplant it. The most frequently indicated storage media for avulsed teeth were nonphysiological media (69.42%). Conclusions The educational level of the community health workers somehow influenced their knowledge (P < 0.001) and attitude (P = 0.016) regarding dental injuries. Educational programs for this group are needed to improve the management of traumatic dental injuries.
TSHB mRNA is linked to cholesterol metabolism in adipose tissue

Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid‐stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross‐sectionally, AT TSH‐β (TSHB) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined. The bidirectional relationship between cholesterol and TSHB were studied in isolated human adipocytes. TSHB mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total‐ and LDL‐cholesterol, and with AT‐specific cholesterol metabolism‐associated lipids [arachidonoyl cholesteryl ester, C8‐dihydroceramide, N‐stearoyl‐d‐sphingosine, and GlcCer(18:0,24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased TSHB mRNA in human AT, whereas excess cholesterol up‐regulated TSHB mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased HMGCR mRNA levels in human adipocytes. In mice, subcutaneous AT Tshb expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of TSHB as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT. —Moreno‐Navarrete, J. M. , Moreno, M. , Ortega, F. , Xifra, G. , Hong, S. , Asara, J. M. , Serrano, J. C. E. , Jové, M. , Pissios, P., Blüher, M. , Ricart, W. , Portero‐Otin, M. , Fernández‐Real, J. M. TSHB mRNA is linked to cholesterol metabolism in adipose tissue. FASEB J. 31, 4482–4491 (2017). www.fasebj. org
Atmospheric ammonia and particulate inorganic nitrogen over the United States

Abstract. We use in situ observations from the Interagency Monitoring of PROtected Visual Environments (IMPROVE) network, the Midwest Ammonia Monitoring Project, 11 surface site campaigns as well as Infrared Atmospheric Sounding Interferometer (IASI) satellite measurements with the GEOS-Chem model to investigate inorganic aerosol loading and atmospheric ammonia concentrations over the United States. IASI observations suggest that current ammonia emissions are underestimated in California and in the springtime in the Midwest. In California this underestimate likely drives the underestimate in nitrate formation in the GEOS-Chem model. However in the remaining continental United States we find that the nitrate simulation is biased high (normalized mean bias > = 1.0) year-round, except in Spring (due to the underestimate in ammonia in this season). None of the uncertainties in precursor emissions, the uptake efficiency of N 2 O 5 on aerosols, OH concentrations, the reaction rate for the formation of nitric acid, or the dry deposition velocity of nitric acid are able to explain this bias. We find that reducing nitric acid concentrations to 75% of their simulated values corrects the bias in nitrate (as well as ammonium) in the US. However the mechanism for this potential reduction is unclear and may be a combination of errors in chemistry, deposition and sub-grid near-surface gradients. This "updated" simulation reproduces PM and ammonia loading and captures the strong seasonal and spatial gradients in gas-particle partitioning across the United States. We estimate that nitrogen makes up 15−35% of inorganic fine PM mass over the US, and that this fraction is likely to increase in the coming decade, both with decreases in sulfur emissions and increases in ammonia emissions.
SIRT1 increases cardiomyocyte binucleation in the heart development

SIRT1 regulates cell senescence. We investigated a novel role of SIRT1 in the regulation of cardiomyocyte terminal differentiation in the developing heart. Retinoic acid (RA)-induced binucleation of H9c2 cells was associated with increased SIRT1 expression. Inhibition of SIRT1 activity or expression significantly decreased RA-induced binucleation. SIRT1 expression was minimal in the fetal heart and significantly upregulated in the hearts of postnatal day 7 (P7) rat pups. In contrast, heart-specific miR-133a expression was high in the fetal heart but significantly reduced in P7 pup hearts. The miR-133a promoter contains a canonical HRE element and hypoxia upregulated miR-133a gene expression in the heart. SIRT1 mRNA 3′UTR has miR-133a binding sequences and miR-133a and hypoxia suppressed SIRT1 expression in cardiomyocytes. Of importance, inhibition of SIRT1 significantly reduced binucleated cardiomyocytes in the hearts of P7 pups. Taken together, the present study reveals a novel role of SIRT1 and its regulation by miR-133a in cardiomyocyte terminal differentiation of the developing heart, and suggests a potential therapeutic strategy that may impact cardiac function later in life.
Is a Picture Worth a Thousand Words? Few Evidence-Based Features of Dietary Interventions Included in Photo Diet Tracking Mobile Apps for Weight Loss

Background: Apps using digital photos to track dietary intake and provide feedback are common, but currently there has been no research examining what evidence-based strategies are included in these apps. Methods: A content analysis of mobile apps for photo diet tracking was conducted, including whether effective techniques for interventions promoting behavior change, including self-regulation, for healthy eating (HE) are targeted. An initial search of app stores yielded 34 apps (n = 8 Android and Apple; n = 11 Android; n = 15 Apple). One app was removed (unable to download), and other apps (n = 4) were unable to be rated (no longer available). Remaining apps (n = 29) were downloaded, reviewed, and coded by 2 independent reviewers to determine the number of known effective self-regulation and other behavior change techniques included. The raters met to compare their coding of the apps, calculate interrater agreement, resolve any discrepancies, and come to a consensus. Results: Six apps (21%) did not utilize any of the behavior change techniques examined. Three apps (10%) provided feedback to users via crowdsourcing or collective feedback from other users and professionals, 7 apps (24%) used crowdsourcing or collective feedback, 1 app (3%) used professionals, and 18 apps (62%) did not provide any dietary feedback to users. Conclusion: Few photo diet-tracking apps include evidence-based strategies to improve dietary intake. Use of photos to self-monitor dietary intake and receive feedback has the potential to reduce user burden for self-monitoring, yet photo diet tracking apps need to incorporate known effective behavior strategies for HE, including self-regulation.
Managerial coaching: challenges, opportunities and training

Purpose – The purpose of this paper is to provide insights into the growing practice of managerial coaching. Much of the coaching literature is set in the context of an external coach coming into an organisation. However managers are increasingly being expected to coach their employees, a change in role which can create tensions.Design/methodology/approach – This paper examines the literature on coaching managers. The paper also discusses practical implications for coach training.Findings – This paper identifies key differences in the issues faced by coaching managers and by internal/external coaches and recognises the importance of adequate training of managers in coaching skills as an important issue for organizations to tackle. Furthermore, the development of a supportive coaching culture should not be underestimated in facilitating managers to apply their coaching skills on a daily basis.Originality/value – The paper gives an overview of the challenges of the coaching managers, identifies areas for de.
Preoperative left ventricular hypertrophy is associated with reduced patient survival after liver transplantation

Left ventricular hypertrophy (LVH) has been described in the context of cirrhotic cardiomyopathy. The influence of LVH on survival of liver transplant (LT) recipients has not been clarified. Therefore, we evaluated the effect of LVH on survival in LT recipients. In total, data from 352 LT patients were analyzed. LVH was diagnosed by echocardiographic measurement of left ventricular wall thickness before LT. Patients were followed up for a mean of 4.2 yr. LVH was diagnosed in 135 (38.4%) patients. Patients with LVH had significantly more frequently male gender (p = 0.046), diastolic dysfunction (p < 0.001), and hepatocellular carcinoma (HCC; p = 0.004). Furthermore, LVH patients were older (p < 0.001) and had a higher body mass index (BMI; p = 0.001). There was no difference in frequency of arterial hypertension, pre‐transplant diabetes mellitus, or etiology of liver cirrhosis. Patients without LVH had a better survival (log rank: p = 0.05) compared with LVH patients. In a multivariate Cox regression LVH (p = 0.031), end‐stage renal disease (ESRD; p = 0.003) and lack of arterial hypertension (p = 0.004) but not MELD score (p = 0.885) were associated with poorer survival.