Miracle-dz/UniFAR-FTUs huggingface dataset:
The relation between birthweight, childhood body mass index, and overweight and obesity in late adolescence: a longitudinal cohort study from Norway, The Tromsø Study, Fit Futures

Objectives Childhood overweight/obesity is associated with later overweight/obesity. However, the association between birth weight and later overweight/obesity has not been established. The aim of this study was to investigate the relation between both birth weight and childhood body mass index (BMI), and adolescent overweight/obesity in a Norwegian population. Methods The Tromsø Study – Fit Futures is a population-based cohort study conducted in 2010–2011 and 2012–2013 in Tromsø, Norway. A representative sample of 961 adolescents participated. Longitudinal anthropometric data were obtained from the Medical Birth Registry of Norway, childhood health records at 2–4 and 5–7 years of age, and repeated measurements at 15–18 and 18–20 years of age. Outcome was defined as normal weight (adult BMI <25 kg/m2) or overweight/obese (adult BMI ≥2 5 kg/m2) at 15–20 years of age according to international age- and sex-specific cut-off values for children. Associations were investigated using generalised estimating equations. Results In adjusted analyses, a 1-SD (586 g) higher birth weight was associated with a higher OR for overweight/obesity at 15–20 years of age (OR 1.25, 95% CI 1.06 to 1.48). Childhood BMI was also associated with overweight/obesity at 15–20 years of age: a 1-SD (1.35 kg/m2) increase in BMI at age 2–4 years rendered an OR of 1.66 (95% CI 1.40 to 1.96); a 1-SD (1.83 kg/m2) increase in BMI at age 5–7 years rendered an OR of 3.23 (95% CI 2.56 to 4.07). When compared with normal-weight children, those with severe overweight/obesity in childhood (adult BMI ≥27 kg/m2) showed stronger associations with overweight/obesity at 15–20 years of age: OR 3.01 (95% CI 1.47 to 6.18) and OR 11.51 (95% CI 6.63 to 19.99) at ages 2–4 and 5–7, respectively. Conclusion Associations between birth weight and overweight/obesity at 15–20 years of age were modest, whereas the influence of BMI at 2–4 and 5–7 years on overweight/obesity at 15–20 years was moderate to strong.
Leadership and Affect: Moving the Hearts and Minds of Followers

We provide an integrative review of the empirical literature on leadership and affect (emotion, mood, and affective dispositions), which is first and foremost a literature on leader displays of affect. We conclude that the influence of leader affective displays can be understood through the mediation paths of emotional contagion and cognitive interpretation of affect in combination with the first- and second-stage moderators of these paths. We also conclude that the common yet overly simplistic notion that leader displays of positive affect are more effective than leader displays of negative affect can in important part be attributed to an overreliance on subjective ratings as indicators of leadership effectiveness, whereas behavioral indicators of leadership effectiveness suggest a more contingent view of the effectiveness of positive and negative affective displays. We propose that to bolster and further develop these conclusions, we need (a) more research focusing on moderation in dual-path mediation; (b) development of theory about cognitive interpretations following leader affective displays; and (c) more sophisticated models of the difference amongst different affective states to better capture the complexity of their effects. We also outline how evidence regarding the role of follower affect in response to leadership more generally points to the potential for integration of affective and non-affective models of leadership.
Structural studies on amorphous silicon boron nitride Si3B3N7: neutron contrast technique on nitrogen and high energy X-ray diffraction

The structure of the new ternary amorphous nitride Si3B3N7, synthesised from the single source precursor TADB [(trichlorosilyl)aminodichloroborane], has been investigated by means of X-ray diffraction using high energy synchrotron radiation and by neutron diffraction using the isotopic contrast technique on nitrogen. The X-ray results have been compared with results from electron diffraction experiments, confirming the trigonal planar coordination of boron (RBN = 1.4 A, ZBN = 2.8, ZNB = 1.2) by nitrogen and the tetrahedral coordination of silicon (RSiN = 1.7 A, ZSiN = 3.8, ZNSi = 1.6) by nitrogen. The neutron contrast technique was applied in order to obtain detailed information about the nitrogen environment. From the total pair correlation functions the N–N distances within the boron and silicon coordination polyhedra could be extracted [RNN(B) = 2.5 A, RNN(Si) = 2.8 A]. In addition, the difference function shows two distinct maxima at ca. 3.8 and 4.3 A in the third coordination sphere resulting from Si–N or B–N pairs connected via three bonds. If at least two of these are B–N bonds a contribution to the first peak results, while the second maximum is matched if at least two Si–N bonds are involved.
Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells

We report the design, synthesis, and biological evaluation of some potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumors, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229. The design of these molecules was informed and supported by X-ray crystal structures. Compound 1 (EG01377) was identified as having properties suitable for further investigation. Compound 1 was then tested in several in vitro assays and was shown to have antiangiogenic, antimigratory, and antitumor effects. Remarkably, 1 was shown to be selective for NRP1 over the closely related protein NRP2. In purified Nrp1+, FoxP3+, and CD25+ populations of Tregs from mice, 1 was able to block a glioma-conditioned medium-induced increase in TGFβ production. This comprehensive characterization of a small-molecule NRP1 antagonist provides the basis for future in vivo studies.
A Cyclin-Binding Motif in Human SAMHD1 Is Required for Its HIV-1 Restriction, dNTPase Activity, Tetramer Formation, and Efficient Phosphorylation

ABSTRACT Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) regulates intracellular deoxynucleoside triphosphate (dNTP) levels and functions as a retroviral restriction factor through its dNTP triphosphohydrolase (dNTPase) activity. Human SAMHD1 interacts with cell cycle regulatory proteins cyclin A2, cyclin-dependent kinase 1 (CDK1), and CDK2. This interaction mediates phosphorylation of SAMHD1 at threonine 592 (T592), which negatively regulates HIV-1 restriction. We previously reported that the interaction is mediated, at least in part, through a cyclin-binding motif (RXL, amino acids [aa] 451 to 453). To understand the role of the RXL motif in regulating SAMHD1 activity, we performed structural and functional analyses of RXL mutants and the effect on HIV-1 restriction. We found that the RXL mutation (R451A and L453A, termed RL/AA) disrupted SAMHD1 tetramer formation and abolished its dNTPase activity in vitro and in cells. Compared to wild-type (WT) SAMHD1, the RL/AA mutant failed to restrict HIV-1 infection and had reduced binding to cyclin A2. WT SAMHD1 and RL/AA mutant proteins were degraded by Vpx from HIV-2 but were not spontaneously ubiquitinated in the absence of Vpx. Analysis of proteasomal and autophagy degradation revealed that WT and RL/AA SAMHD1 protein levels were enhanced only when both pathways of degradation were simultaneously inhibited. Our results demonstrate that the RXL motif of human SAMHD1 is required for its HIV-1 restriction, tetramer formation, dNTPase activity, and efficient phosphorylation at T592. These findings identify a new functional domain of SAMHD1 important for its structural integrity, enzyme activity, phosphorylation, and HIV-1 restriction. IMPORTANCE SAMHD1 is the first mammalian dNTPase identified as a restriction factor that inhibits HIV-1 replication by decreasing the intracellular dNTP pool in nondividing cells, although the critical mechanisms regulating SAMHD1 function remain unclear. We previously reported that mutations of a cyclin-binding RXL motif in human SAMHD1 significantly affect protein expression levels, half-life, nuclear localization, and phosphorylation, suggesting an important role of this motif in modulating SAMHD1 functions in cells. To further understand the significance and mechanisms of the RXL motif in regulating SAMHD1 activity, we performed structural and functional analyses of the RXL motif mutation and its effect on HIV-1 restriction. Our results indicate that the RXL motif is critical for tetramer formation, dNTPase activity, and HIV-1 restriction. These findings help us understand SAMHD1 interactions with other host proteins and the mechanisms regulating SAMHD1 structure and functions in cells.
Genetics in the prevention and management of coronary artery disease

Purpose of review The current review is to describe the genetic risk variants that have been discovered predisposing to coronary artery disease (CAD) and how they are utilized to stratify for risk of CAD. Recent findings Over 90 genetic risk variants have been discovered that predispose to risk for CAD. Summary The total genetic risk burden for CAD is proportional to the number of risk variants inherited and can be combined into a single number referred to as the genetic risk score (GRS). GRS has been utilized in multiple studies and shown to be more effective in risk stratification for CAD than conventional risk factors. There is a major advantage to risk stratification based on the GRS since the risk can be determined at birth or anytime throughout one's lifetime since the individual's DNA does not change. Widespread application of the GRS is likely to enable a paradigm shift in the primary prevention of CAD.
A faster escape does not enhance survival in zebrafish larvae

An escape response is a rapid manoeuvre used by prey to evade predators. Performing this manoeuvre at greater speed, in a favourable direction, or from a longer distance have been hypothesized to enhance the survival of prey, but these ideas are difficult to test experimentally. We examined how prey survival depends on escape kinematics through a novel combination of experimentation and mathematical modelling. This approach focused on zebrafish (Danio rerio) larvae under predation by adults and juveniles of the same species. High-speed three-dimensional kinematics were used to track the body position of prey and predator and to determine the probability of behavioural actions by both fish. These measurements provided the basis for an agent-based probabilistic model that simulated the trajectories of the animals. Predictions of survivorship by this model were found by Monte Carlo simulations to agree with our observations and we examined how these predictions varied by changing individual model parameters. Contrary to expectation, we found that survival may not be improved by increasing the speed or altering the direction of the escape. Rather, zebrafish larvae operate with sufficiently high locomotor performance due to the relatively slow approach and limited range of suction feeding by fish predators. We did find that survival was enhanced when prey responded from a greater distance. This is an ability that depends on the capacity of the visual and lateral line systems to detect a looming threat. Therefore, performance in sensing, and not locomotion, is decisive for improving the survival of larval fish prey. These results offer a framework for understanding the evolution of predator–prey strategy that may inform prey survival in a broad diversity of animals.
Longitudinal Links Between Work Experiences and Marital Satisfaction in African American Dual-Earner Couples

This study assessed associations between both work demands (pressure, hours) and work resources (self-direction) and marital satisfaction in a sample of 164 African American dual-earner couples who were interviewed annually across 3 years. Grounded in the work–home resources and family systems frameworks, results from longitudinal actor–partner interdependence models (APIM) revealed main effects of spouses’ work experiences on their own marital satisfaction, but these effects were qualified by the interactive effects of spouses’ and partners’ work experiences. Some interactive effects were consistent with an amplifying pattern, for example that, beyond the main effects of actor self-direction, marital satisfaction was highest when both spouses experienced high work self-direction. Other effects were consistent with a comparative pattern, such that shorter work hours were linked to lower marital satisfaction only when partners worked longer hours. Gender moderation also was evident in findings that wives’ work pressure was negatively linked to marital satisfaction only when their husbands reported high pressure, but husbands’ work pressure was negatively linked to marital satisfaction only when their wives reported low pressure. This study advances understanding of work–marriage linkages in African American couples, an understudied group with a distinctive connection to the labor force. Analyses demonstrate what can be learned from investigating the couple as a unit and illustrate how family systems concepts can be addressed via APIM.
An Exploration of the Determinants of Gestational Weight Gain in African American Women: Genetic Factors and Energy Expenditure

Background: Excessive gestational weight gain (GWG) has a long-term impact on women’s body weight and contributes to the development of obesity in the mother and her child. Many risk factors for GWG have been identified, but to date, only 6–33.8% of the variance in GWG has been explained. The purpose of this study was to evaluate the overall variance of GWG that can be explained by including weight-adjusted resting metabolic rate (aRMR) and a genetic risk score constructed on obesity-related genes in addition to sociodemographic and lifestyle factors. Methods: In this observational study involving 55 African American women, data collected/measured during pregnancy included sociodemographic factors, medical information, lifestyle factors, aRMR, and seven obesity-related genes. Multivariable linear regression was performed to evaluate the variance in GWG explained by the potential risk factors listed above. Results: The mean GWG was 15 kg (±7.5 kg), and 63.6% of women gained more than the Institute of Medicine’s GWG recommendations. The final regression model explained 53.3% of the variance in GWG. Higher genetic risk score, lower aRMR, and higher dietary intake of total energy and percentage of fat were significantly associated with increased GWG (p < .05). These factors explained 18% additional variance in GWG over that explained by significant sociodemographic and lifestyle factors in the analysis (i.e., maternal age, prepregnancy body mass index, parity, illegal drug use, and education). Conclusion: Overall, our results indicate that the genetic risk score, aRMR, and dietary intake have a substantial impact on GWG in African American women.
Lupus community panel proposals for optimising clinical trials: 2018

Formidable impediments stand in the way of treatment development for lupus. These include the unwieldy size of current trials, international competition for scarce patients, complex outcome measures and a poor understanding of these outcomes in the world at large. The heterogeneity of the disease itself coupled to superimposition of variegated background polypharmacy has created enough immunological noise to virtually ensure the failure of lupus treatment trials, leaving an understandable suspicion that at least some of the results in testing failed drugs over the years may not have been negative, but merely uninterpretable. The authors have consulted with many clinical trial investigators, biopharmaceutical developers and stakeholders from government and voluntary sectors. This paper examines the available evidence that supports workable trial designs and proposes approaches to improve the odds of completing interpretable treatment development programs for lupus.
Assessment of cadmium and its impact on the uptake efficiency of Phosphate fertilizers by Amaranthus tricolour

Phosphorus is a most essential plant nutrient; its deficiency in soils is severely affecting the growth of crop production. A batch mode RBD (Randomized block design) study was carried out to assess the efficiency of water and citric acid soluble various phosphate fertilizers in soils and their uptake efficiency by using the plant, Amaranthus tricolour variety. The various soil samples are analyzed before and after the application of fertilizer. The leaf (green and dry) samples of the plant at two different growth stages (20 & 35 days) of plant and dry matter production (20 & 35 days) of plant were collected, analyzed, calculated and expressed in t/ha. The performance of each fertilizer and their efficiency were assessed by applying various quantities of phosphate fertilizers and its results of the study showed that the presence of toxic metals like cadmium in the soils has been reduces nutrient uptake capacity of the plant considerably. This trend was increases with the accumulation of more stable forms of cadmium in the soil. The observed results indicate that the uptake efficiency of phosphate fertilizers increases with applying very high quantity of phosphate in the presence of cadmium. The action of cadmium is seen at the whole plant level in reduced growth.
Appropriate Use of Prophylactic Antibiotic Agents in Gynecologic Surgeries at a Midwestern Teaching Hospital.

BACKGROUND The purpose of this study was to establish compliance with guidelines published by the American College of Obstetricians and Gynecologists (ACOG) regarding prophylactic antibiotic use in gynecologic surgery at our institution, and define areas of improvement to promote antibiotic stewardship. PATIENTS AND METHODS This was a retrospective cohort study at a single, large tertiary care and teaching hospital in Kansas. Patients who underwent inpatient or outpatient gynecologic surgery during 2013 were included. Based on published guidelines for prophylactic antibiotic agents for gynecologic surgery by ACOG, procedures were classified as antibiotic-indicated or antibiotic-not-indicated. Chi-square and Fisher exact test analysis were used to identify factors associated with antibiotic use. RESULTS Of the 1,735 cases eligible for inclusion, 1,045 (60.2%) had antibiotic agents recommended per guidelines, and appropriate antibiotic agents were given in 1,031 (98.7%) of those cases. In 690 (39.8%) cases, prophylactic antibiotics were either not recommended or the guidelines are not well defined. Of the 690 cases without indication for antibiotic agents, 394 (57.1%) received prophylactic antibiotic agents. Agreement with guidelines varied substantially based on patient age, race, insurance status, area of residence, and if the procedure was a resident case (p < 0.05). Myomectomy, laparoscopy, and ectopic pregnancy procedures received antibiotic agents against recommendations 96.3%, 75.6%, and 45.5% of the time, respectively. CONCLUSIONS Peri-operative antibiotics are often administered inappropriately to women undergoing gynecologic surgeries for which published guidelines are not well defined. Future studies need to identify strategies to reduce antibiotic use in surgical procedures unlikely to benefit from prophylaxis.
Cost-Effectiveness of Tdap Vaccination of Adults Aged ≥65 Years in the Prevention of Pertussis in the US: A Dynamic Model of Disease Transmission

Objectives In February 2012, the Advisory Committee on Immunization Practices (ACIP) advised that all adults aged ≥65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap), expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged ≥65 to “baseline” practice [full-strength DTaP administered from 2 months to 4–6 years, and one dose of Tdap at 11–64 years replacing decennial Td booster], using a dynamic model. Methods We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged ≥65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care) and quality-adjusted life-years (QALYs) associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges. Results For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants) of pertussis annually at steady state. Additional vaccination costs are $4.7 million. Net cost savings, including vaccination costs, are $47.7 million (societal perspective) and $44.8 million (payer perspective). From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs) versus baseline. Results are robust to sensitivity analyses and alternative scenarios. Conclusions Immunization of eligible adults aged ≥65, consistent with the current ACIP recommendation, is cost saving from both payer and societal perspectives.
Experiences of Gender-Based Violence at a South African University: Prevalence and Effect on Rape Myth Acceptance

Instances of gender-based violence (GBV) on university campuses are rarely reported to the authorities. This makes it difficult to gauge the prevalence of this problem, which in turn affects efforts for prevention. This article describes a university-wide online survey aimed at assessing, first, the prevalence of GBV experienced by the three sectors in the community—students, academic and research staff, and professional/administrative staff. Many of the findings concurred with research elsewhere—students were the predominant victims of GBV; men were the main perpetrators; and instances of rape occurred mainly when the victim/survivor was under the influence of alcohol or drugs. In contrast to some of the more well-known U.S. surveys (e.g., Georgetown University), we found relatively few instances of students being exploited by staff members. Occurrences of contrapower harassment were also reported in our survey. The second aim investigated whether rape myth acceptance was related to experiences of GBV. We found that women who had these experiences were more rejecting of rape myths than women who had not had such experiences. The opposite was found for White men. White men who had experienced GBV were more accepting of the rape myths than those who had not had such experiences. It was suggested that this reflected a need for these male victims to establish their hegemonic masculine identity. In general, the level of rape myth acceptance was relatively low. This suggested that widespread victim-blame, and self-blame does not account for the low levels of GBV reports to officials. A limitation of the study was the relatively low response rate (1,350 respondents), which was likely caused by the student protests over university fees that were ongoing at the time of the survey. These protests caused considerable disturbance for all sectors of the university community.