Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of the objective built environment along the route to school with children’s modes of commuting: A multilevel modelling analysis (the SLIC study)

As active commuting levels continue to decline among primary schoolchildren, evidence about which built environmental characteristics influence walking or cycling to school remains inconclusive and is strongly context-dependent. This study aimed to identify the objective built environmental drivers of, and barriers to, active commuting to school for a multi-ethnic sample of 1,889 healthy primary schoolchildren (aged 5–11) in London, UK. Using cross-sectional multilevel ordered logistic regression modelling, supported by the spatial exploration of built environmental characteristics through cartography, the objective built environment was shown to be strongly implicated in children’s commuting behaviour. In line with earlier research, proximity to school emerged as the prime variable associated with the choice for active commuting. However, other elements of the urban form were also significantly associated with children’s use of active or passive modes of transport. High levels of accidents, crime and air pollution along the route to school were independently correlated with a lower likelihood of children walking or cycling to school. Higher average and minimum walkability and higher average densities of convenience stores along the way were independently linked to higher odds of active commuting. The significance of the relations for crime, air pollution and walkability disappeared in the fully-adjusted model including all built environmental variables. In contrast, relationships with proximity, traffic danger and the food environment were maintained in this comprehensive model. Black children, pupils with obesity, younger participants and those from high socioeconomic families were less likely to actively commute to school. There is thus a particular need to ensure that roads with high volumes of actively commuting children are kept safe and clean, and children’s exposure to unhealthy food options along the way is limited. Moreover, as short commuting distances are strongly correlated with walking or cycling, providing high-quality education near residential areas might incite active transport to school.
Sex of Walker Influences Scent-marking Behavior of Shelter Dogs

Simple Summary In diverse settings, human presence and handling influence the behavior and physiology of other animals, often causing increased vigilance and stress, especially if the human is unfamiliar. Domestic dogs are unusual in that human interaction often reduces stress and behavioral signs of stress. Nevertheless, there is some evidence that the sex of an unfamiliar person can influence canine behavior. To determine whether sex of an unfamiliar walker might influence the behavior of dogs at an animal shelter, we observed 100 dogs during leash walks and recorded all occurrences of scent-marking behaviors. Male dogs urinated at higher rates when walked by unfamiliar women than when walked by unfamiliar men. Female dogs urinated at similar rates when walked by unfamiliar men and unfamiliar women. Sex of walker also influenced urinary posture in male dogs. Both male and female dogs were more likely to defecate when walked by unfamiliar women than when walked by unfamiliar men. Based on our findings, and those of others, we suggest that the sex of all observers and handlers be reported in behavioral studies of dogs and considered in behavioral evaluations at animal shelters, where results can impact whether or not a dog is made available for adoption. Abstract Interactions with humans influence the behavior and physiology of other animals, and the response can vary with sex and familiarity. Dogs in animal shelters face challenging conditions and although contact with humans typically reduces stress and behaviors associated with stress, evidence indicates that shelter dogs react differently to unfamiliar men and women. Given that some aspects of canine scent-marking behavior change under fearful conditions, we examined whether sex of an unfamiliar walker would influence scent-marking behavior of 100 shelter dogs during leash walks. Male dogs urinated at higher rates when walked by unfamiliar women than when walked by unfamiliar men; female dogs urinated at similar rates when walked by unfamiliar women and unfamiliar men. Sex of walker influenced urinary posture in male dogs, but not in female dogs. Both male and female dogs were more likely to defecate when walked by unfamiliar women than by unfamiliar men. Based on our findings that shelter dogs behave differently in the presence of unfamiliar men and women, we suggest that researchers conducting behavioral studies of dogs record, consider in analyses, and report the sex of observers and handlers as standard practice. We also recommend recording the sex of shelter staff present at behavioral evaluations because the results of these evaluations can impact dog welfare.
Does Estimated Pulse Wave Velocity Add Prognostic Information?

Supplemental Digital Content is available in the text. The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell’s C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20–1.25] per m/s or 1.32 [1.29–1.34]), cardiovascular mortality (1.26 [1.21–1.32] or 1.35 [1.31–1.40]), and composite cardiovascular end point (1.19 [1.16–1.22] or 1.23 [1.20–1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08–1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91–1.03]) nor composite cardiovascular end point (1.10 [0.97–1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.
Genetic ablation of the mitoribosome in the malaria parasite Plasmodium falciparum sensitizes it to antimalarials that target mitochondrial functions

The mitochondrion of malaria parasites contains several clinically validated drug targets. Within Plasmodium spp. , the causative agents of malaria, the mitochondrial DNA (mtDNA) is only 6 kb long, being the smallest mitochondrial genome among all eukaryotes. The mtDNA encodes only three proteins of the mitochondrial electron transport chain and ∼27 small, fragmented rRNA genes having lengths of 22–195 nucleotides. The rRNA fragments are thought to form a mitochondrial ribosome (mitoribosome), together with ribosomal proteins imported from the cytosol. The mitoribosome of Plasmodium falciparum is essential for maintenance of the mitochondrial membrane potential and parasite viability. However, the role of the mitoribosome in sustaining the metabolic status of the parasite mitochondrion remains unclear. The small ribosomal subunit in P. falciparum has 14 annotated mitoribosomal proteins, and employing a CRISPR/Cas9-based conditional knockdown tool, here we verified the location and tested the essentiality of three candidates (PfmtRPS12, PfmtRPS17, and PfmtRPS18). Using immuno-EM, we provide evidence that the P. falciparum mitoribosome is closely associated with the mitochondrial inner membrane. Upon knockdown of the mitoribosome, parasites became hypersensitive to inhibitors targeting mitochondrial Complex III (bc1), dihydroorotate dehydrogenase (DHOD), and the F1F0-ATP synthase complex. Furthermore, the mitoribosome knockdown blocked the pyrimidine biosynthesis pathway and reduced the cellular pool of pyrimidine nucleotides. These results suggest that disruption of the P. falciparum mitoribosome compromises the metabolic capacity of the mitochondrion, rendering the parasite hypersensitive to a panel of inhibitors that target mitochondrial functions.
Impact of Urbanization and Economic Growth on CO2 Emission: A Case of Far East Asian Countries

Rising CO2 emission constitute a great threat to the world environment and public health. This study examines the major determinants of CO2 emissions in Far East countries in the period of 1980 to 2017. We adopt a panel data-fixed effect model that accounts for time-invariant country-specific characteristics that may create omitted-variable bias. We also additionally take care of the time trend by applying an annual fixed effect into our model. The study finds that urbanization, economic growth and trade openness significantly determine CO2 emission in the selected countries. Thus, the main policy suggestions are (a) to encourage green and sustainable urbanization, as it helps in economic progress but not at the expense of environmental deterioration; (b) to strategically regulate and improve industrial structure; and (c) enhance sharing of renewable energy in total energy consumption.
New Insights into 4-Anilinoquinazolines as Inhibitors of Cardiac Troponin I–Interacting Kinase (TNNi3K)

We report the synthesis of several related 4-anilinoquinazolines as inhibitors of cardiac troponin I–interacting kinase (TNNi3K). These close structural analogs of 3-((6,7-dimethoxyquinazolin-4-yl)amino)-4-(dimethylamino)-N-methylbenzenesulfonamide (GSK114) provide new understanding of structure–activity relationships between the 4-anilinoquinazoline scaffold and TNNi3K inhibition. Through a small focused library of inhibitors, we observed that the N-methylbenzenesulfonamide was driving the potency in addition to the more traditional quinazoline hinge-binding motif. We also identified a compound devoid of TNNi3K kinase activity due to the addition of a methyl group in the hinge binding region. This compound could serve as a negative control in the study of TNNi3K biology. Small molecule crystal structures of several quinazolines have been solved, supporting observations made about overall conformation and TNNi3K inhibition.
EARSHOT: A Minimal Neural Network Model of Incremental Human Speech Recognition

Despite the lack of invariance problem (the many-to-many mapping between acoustics and percepts), human listeners experience phonetic constancy and typically perceive what a speaker intends. Most models of human speech recognition (HSR) have side-stepped this problem, working with abstract, idealized inputs and deferring the challenge of working with real speech. In contrast, carefully engineered deep learning networks allow robust, real-world automatic speech recognition (ASR). However, the complexities of deep learning architectures and training regimens make it difficult to use them to provide direct insights into mechanisms that may support HSR. In this brief article, we report preliminary results from a two-layer network that borrows one element from ASR, long short-term memory nodes, which provide dynamic memory for a range of temporal spans. This allows the model to learn to map real speech from multiple talkers to semantic targets with high accuracy, with human-like timecourse of lexical access and phonological competition. Internal representations emerge that resemble phonetically organized responses in human superior temporal gyrus, suggesting that the model develops a distributed phonological code despite no explicit training on phonetic or phonemic targets. The ability to work with real speech is a major advance for cognitive models of HSR.
A Comparative Study of Brachial–Ankle Pulse Wave Velocity and Heart–Finger Pulse Wave Velocity in Korean Adults

Arterial stiffness is considered an index of vascular aging. The brachial–ankle pulse wave velocity (baPWV) method is widely used because of its proven effectiveness; and the pulse wave velocity measurement method using both electrocardiogram (ECG) and photoplethysmogram (PPG) is actively being studied due to the convenience of measurement and the possibility of miniaturization. The aim of this study was to evaluate and compare the effects of age and gender in Korean adults using both the baPWV method and the PWV method with ECG and finger PPG (heart–finger PWV). The measurements have been carried out for 185 healthy subjects of Korean adults, and the results showed that the baPWV was highly correlated with age in both genders (r = 0.94 for both males and females). However, the correlation values in heart–finger PWV measurement were significantly lower than those of baPWV (r = 0.37 for males and r = 0.71 for females). Although the heart–finger PWV method is suitable for mobile applications because it can be easily miniaturized while maintaining its signal quality, these results show that the heart–finger PWV method is not as effective as baPWV at evaluating the arterial stiffness.
Effect of Stress Management Training on Stigma and Social Phobia in HIV-Positive Women

The purpose of this study was to investigate the effect of stress management training on stigma and social phobia among HIV-positive women. This quasi-experimental pre- and posttest study was performed on a single group of 55 HIV-positive females Hamadan city, Iran, in 2018. The samples were taken through a convenience sampling method and the data collection tool were Berger HIV Stigma and Connor Social Phobia Scale. The mean scores of the stigma were 119.98 ± 21.15 and 94.78 ± 16.34 and social phobia were 24 ± 17.4 and 11.2 ± 9.68 before and after the intervention, respectively. The results of the paired sample t test indicated a significant difference in the stigma and social phobia mean scores before and after the intervention in HIV-positive women (P < .05). The results of the study revealed that stigma and social phobia are big challenges for HIV-positive women since these people are always judged by others and are subjected to labeling and rejection.
The clinical feature of silent infections of novel coronavirus infection (COVID‐19) in Wenzhou

Here were reported clinical features of silent infected COVID-19 patients. Our study showed that the prevalence of the silent infection of COVID-19 is 5.8% (95% CI: 3.4-9.9%), which is much higher than 1.2% which from the report in China CDC. The silent infection patients were more likely to be young adults, the patients without chronic disease. All of the cases in the presented study was found because they were traced as close contact of confirmed cases. Our study indicated that traced the close contract of confirmed case, long time self-quarantine, and screening is necessary to prevent the secondary cases in community. This article is protected by copyright. All rights reserved.
IL (Interleukin)-1 Receptor Antagonist Increases Ang (Angiotensin [1–7]) and Decreases Blood Pressure in Obese Individuals

Supplemental Digital Content is available in the text. IL (Interleukin)-1 antagonism decreases blood pressure in obese individuals. The underlying mechanisms are unknown. Based on experimental data, we hypothesized an effect of IL-1 antagonism via modulation of the renin-angiotensin-aldosterone system. In this explorative study, we examined shorter- (2 days) and longer-term effects (4 weeks) of IL-1 antagonism (anakinra/Kineret) on renin-angiotensin system peptide profiles and on hemodynamic parameters assessed by noninvasive measurement in obese (body mass index ≥30 kg/m2) individuals from 2 interventional trials (a prospective interventional trial [n=73] and a placebo controlled-double blinded interventional trial [n=67]). A total of 140 patients were included. Systolic blood pressure decreased after short-term (absolute difference −5.2 mm Hg [95% CI, −8.5 to −1.8]; P=0.0006) and after longer-term treatment with anakinra (absolute difference −3.9 mm Hg [95% CI, −7.59 to −0.21]; P=0.04), with no change in blood pressure in the placebo group. Upon IL-1 antagonism, equilibrium levels of Ang II (angiotensin II), Ang I, aldosterone, and renin remained unchanged. In contrast, Ang (1–7) peptide levels increased after 4 weeks (between-group difference 16.35 pmol/L [95% CI, 1.22–30.17], P=0.03), as well as the Ang (1–7)/Ang II ratio (between-group difference 0.42 [95% CI, 0.17–0.67], P=0.02) in comparison to placebo. Consistently, the stroke systemic vascular resistance index significantly decreased in the anakinra group (between-group difference of −62.65 dyn/sec per cm−5 per m2 [95% CI, −116.94 to −18.36], P=0.008, consistent with a 25% decrease). IL-1 antagonism increased the vasodilatory Ang (1–7) peptide after 4 weeks of treatment in obese individuals, paralleled by a decrease in peripheral vascular resistance. These findings point to an IL-1 mediated blood pressure-lowering mechanism via modulation of Ang (1–7). Registration— URL: https://www.clinicaltrials. gov. Unique identifiers: NCT02227420 and NCT02672592.
PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells

Significance PSGL-1 and CD43 are surface glycoproteins expressed on blood CD4 T cells to bind to selectins for T cell tethering, rolling, and migration into inflamed tissues. The PSGL-1 level is greatly up-regulated during inflammation. Here we found that PSGL-1 and CD43 expression inhibits HIV spreading infection. Mechanistically, PSGL-1 blocks the binding of virus particles to target cells. PSGL-1–mediated suppression of virus infectivity extends to another retrovirus—murine leukemia virus—and to influenza A virus. These results further our understanding of virus–host interactions and help elucidate mechanisms by which cellular host factors regulate viral infection and pathogenesis. P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-like, 120-kDa glycoprotein that binds to P-, E-, and L-selectins. PSGL-1 is expressed primarily on the surface of lymphoid and myeloid cells and is up-regulated during inflammation to mediate leukocyte tethering and rolling on the surface of endothelium for migration into inflamed tissues. Although it has been reported that PSGL-1 expression inhibits HIV-1 replication, the mechanism of PSGL-1–mediated anti-HIV activity remains to be elucidated. Here we report that PSGL-1 in virions blocks the infectivity of HIV-1 particles by preventing the binding of particles to target cells. This inhibitory activity is independent of the viral glycoprotein present on the virus particle; the binding of particles bearing the HIV-1 envelope glycoprotein or vesicular stomatitis virus G glycoprotein or even lacking a viral glycoprotein is impaired by PSGL-1. Mapping studies show that the extracellular N-terminal domain of PSGL-1 is necessary for its anti–HIV-1 activity, and that the PSGL-1 cytoplasmic tail contributes to inhibition. In addition, we demonstrate that the PSGL-1–related monomeric E-selectin–binding glycoprotein CD43 also effectively blocks HIV-1 infectivity. HIV-1 infection, or expression of either Vpu or Nef, down-regulates PSGL-1 from the cell surface; expression of Vpu appears to be primarily responsible for enabling the virus to partially escape PSGL-1–mediated restriction. Finally, we show that PSGL-1 inhibits the infectivity of other viruses, such as murine leukemia virus and influenza A virus. These findings demonstrate that PSGL-1 is a broad-spectrum antiviral host factor with a unique mechanism of action.
Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

The hypothalamic–pituitary–adrenal (HPA) axis plays a critical role in adaptive stress responses and maintaining organism homeostasis. The pituitary corticotroph is the central player in the HPA axis and is regulated by a plethora of hormonal and stress related factors that synergistically interact to activate and temper pro-opiomelanocortin (POMC) transcription, to either increase or decrease adrenocorticotropic hormone (ACTH) production and secretion as needed. Nuclear receptors are a family of highly conserved transcription factors that can also be induced by various physiologic signals, and they mediate their responses via multiple targets to regulate metabolism and homeostasis. In this review, we summarize the modulatory roles of nuclear receptors on pituitary corticotroph cell POMC transcription, describe the unique and complex role these factors play in hypothalamic–pituitary–adrenal axis (HPA) regulation and discuss potential therapeutic targets in disease states.
Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020

As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).