Miracle-dz/UniFAR-FTUs huggingface dataset:
A toolkit for GFP-mediated tissue-specific protein degradation in C. elegans

Proteins that are essential for embryo production, cell division and early embryonic events are frequently reused later in embryogenesis, during organismal development or in the adult. Examining protein function across these different biological contexts requires tissue-specific perturbation. Here, we describe a method that uses expression of a fusion between a GFP-targeting nanobody and a SOCS-box containing ubiquitin ligase adaptor to target GFP-tagged proteins for degradation. When combined with endogenous locus GFP tagging by CRISPR-Cas9 or with rescue of a null mutant with a GFP fusion, this approach enables routine and efficient tissue-specific protein ablation. We show that this approach works in multiple tissues – the epidermis, intestine, body wall muscle, ciliated sensory neurons and touch receptor neurons – where it recapitulates expected loss-of-function mutant phenotypes. The transgene toolkit and the strain set described here will complement existing approaches to enable routine analysis of the tissue-specific roles of C. elegans proteins. Summary: A simple method to target GFP-tagged proteins for proteasomal degradation enables spatially controlled protein elimination in C. elegans.
Adolescent Use of Insulin and Patient-Controlled Analgesia Pump Technology: A 10-Year Food and Drug Administration Retrospective Study of Adverse Events

the case in our study). In fact, the Bocelli et al statement that “a negative FE finding usually does not affect interpretation of CA findings significantly” underscores the message of our study: that there is additional diagnostic utility to be gained from CA even when FE findings are normal. Bocelli et al go on to state that on the basis of the “low prevalence of children with positive FE and negative CA findings . compared with those with negative FE and positive CA findings,” interpretation of our results would result in a “spurious increase in sensitivity” and that “it could be estimated that specificity of FE alone was 97.6%[,] . whereas specificity of the approach combining FE and postnatal CA . was 90.9%. ” As stated in the limitations section of our article, and as acknowledged by Bocelli et al, our study was not designed to evaluate sensitivity/specificity of FE versus FE and CA, because pediatric echocardiography was not routinely performed. Bocelli et al conclude that “taking into account that additional lesions detected by CA and missed by FE were all minor or noncomplex CHD, the opportunity to routinely perform FE followed by postnatal CA in the offspring of women with CHD should be critically considered. ” Although the CHD detected by CA was noncomplex and, therefore, not likely to affect short-term survival, there are important implications regarding need for long-term cardiology follow-up as well as concerns regarding heritability of CHD to be considered at the time of future family planning. We thank Bocelli et al for their interest in our work; we believe that their concerns have been addressed adequately above. Ultimately, the decision to apply our research findings will be impacted by local practice patterns and resource availability, specifically with respect to availability of pediatric cardiologists and/or pediatric echocardiography.
The Cost of Preterm Birth Throughout Childhood in England and Wales

BACKGROUND. Infants born preterm are at increased risk of adverse health and developmental outcomes. Mortality and morbidity after preterm birth impose a burden on finite public sector resources. This study considers the economic consequences of preterm birth from birth to adult life and compares the costs accruing to those born preterm with those born at term. METHODS. A decision-analytic model was constructed to estimate the costs to the public sector over the first 18 years after birth, stratified by week of gestational age at birth. Costs were discounted and reported in UK pounds at 2006 prices. Probabilistic sensitivity analysis was used to examine uncertainty in the model parameters and generate confidence intervals surrounding the cost estimates. RESULTS. The model estimates the costs associated with a hypothetical cohort of 669601 children and is based on live birth and preterm birth data from England and Wales in 2006. The total cost of preterm birth to the public sector was estimated to be £2.946 billion (US $4.567 billion), and an inverse relationship was identified between gestational age at birth and the average public sector cost per surviving child. The incremental cost per preterm child surviving to 18 years compared with a term survivor was estimated at £22885 (US $35471). The corresponding estimates for a very and extremely preterm child were substantially higher at £61781 (US $95760) and £94740 (US $146847), respectively. CONCLUSIONS. Despite concerns about ongoing costs after discharge from perinatal services, the largest contribution to the economic implications of preterm birth are hospital inpatient costs after birth, which are responsible for 92.0% of the incremental costs per preterm survivor.
Delayed male germ cell sex-specification permits transition into embryonal carcinoma cells with features of primed pluripotency

Testicular teratomas result from anomalies in embryonic germ cell development. In 129 inbred mice, teratoma initiation coincides with germ cell sex-specific differentiation and the mitotic-meiotic switch: XX and XY germ cells repress pluripotency, XX germ cells initiate meiosis, and XY germ cells activate male-specific differentiation and mitotic arrest. Here, we report that expression of Nanos2, a gene that is crucial to male sex specification, is delayed in teratoma-susceptible germ cells. Decreased expression of Nanos2 was found to be due, in part, to the Nanos2 allele present in 129 mice. In teratoma-susceptible germ cells, diminished expression of genes downstream of Nanos2 disrupted processes that were crucial to male germ cell differentiation. Deficiency for Nanos2 increased teratoma incidence in 129 mice and induced developmental abnormalities associated with tumor initiation in teratoma-resistant germ cells. Finally, in the absence of commitment to the male germ cell fate, we discovered that a subpopulation of teratoma-susceptible germ cells transition into embryonal carcinoma (EC) cells with primed pluripotent features. We conclude that delayed male germ cell sex-specification facilitates the transformation of germ cells with naïve pluripotent features into primed pluripotent EC cells. Highlighted Article: Delayed male germ cell sex specification facilitates the transformation of germ cells with naïve pluripotent properties into primed pluripotent-like embryonal carcinoma cells, the tumor stem cells of testicular germ cell tumors.
p53: emerging roles in stem cells, development and beyond

ABSTRACT Most human cancers harbor mutations in the gene encoding p53. As a result, research on p53 in the past few decades has focused primarily on its role as a tumor suppressor. One consequence of this focus is that the functions of p53 in development have largely been ignored. However, recent advances, such as the genomic profiling of embryonic stem cells, have uncovered the significance and mechanisms of p53 functions in mammalian cell differentiation and development. As we review here, these recent findings reveal roles that complement the well-established roles for p53 in tumor suppression. Summary: This Primer provides an overview of the roles of p53 in development and stem cells, and highlights how these relate to its well-known functions in tumor suppression.
European perspective on the use of antiplatelet agents in atherothrombotic disease

Platelets are components of normal haemostasis, but under certain circumstances, they contribute to coronary occlusion and myocardial ischaemia. Several drugs have been investigated for decades to modulate platelet adhesion and aggregation in coronary artery disease. Although these drugs improve the symptoms and prognosis of millions of patients by reducing arterial thrombosis, they pose a variable risk of haemorrhagic complications. The European Society of Cardiology has published several recommendations on antiplatelet therapy that will be reviewed in this article, together with data from the real-world daily use of these drugs.
Playing Active Video Games Increases Energy Expenditure in Children

OBJECTIVE: To compare energy expenditure rates in children playing the physically active video games, Dance Dance Revolution (DDR) and Nintendo's Wii Sports in relation to treadmill walking. METHODS: Energy expenditure, heart rate, step rate, and perceived exertion were measured in 14 boys and 9 girls (ages 10–13 years; BMI at 3–98th percentile for age and gender) while watching television at rest, playing DDR at 2 skill levels, playing Wii bowling and boxing, and walking at 2.6, 4.2, and 5.7 km/h. Arterial elasticity was measured at rest and immediately after gaming. RESULTS: Compared with watching television, energy expenditure while gaming or walking increased 2- to 3-fold. Similarly, high rates of energy expenditure, heart rate, and perceived exertion were elicited from playing Wii boxing, DDR level 2, or walking at 5.7 km/h. This occurred despite variations in step rate among activities, reflecting greater use of upper body during Wii play (lowest step rate) than during walking (highest step rate) or DDR play. Wii bowling and beginner level DDR elicited a 2-fold increase in energy expenditure compared to television watching. Large-artery elasticity declined immediately after both DDR and Wii. The change was inversely related to the increment in energy expenditure above rest achieved during the activity. CONCLUSIONS: Energy expenditure during active video game play is comparable to moderate-intensity walking. Thus, for children who spend considerable time playing electronic screen games for entertainment, physically active games seem to be a safe, fun, and valuable means of promoting energy expenditure.
Pervasive game flow: understanding player enjoyment in pervasive gaming

Player enjoyment is perhaps the most important issue in successful game design, but so far it has not been addressed in the area of pervasive games. Departing from the general gameflow model, this article presents an initial outline for a new model of pervasive player enjoyment, that is, the pervasive gameflow model, which is described and discussed in terms of additions and elaborations to the general gameflow model. It is intended to serve as a departure point for further empirical studies on player enjoyment in pervasive games.
Constructing my online self: avatars that increase self-focused attention

Three studies investigated whether users' strategies for customising online avatars increase their self-focused attention, also known as private self-awareness. Study 1 showed that a high number of users adapt their avatars toreflect their own appearance. Study 2 demonstrated that users who perceive their avatars to be similar to their own appearance experience as a result heightened private self-awareness. In Study 3, private self-awareness pervadedsocial interaction taking place over time when users with representative avatars, compared to a control group, reported increased private self-awareness. Drawing from research in interpersonal communication, we suggest that avatars which increase their owners' self-focus may have an influence on online behavior in the context of social computing.
Survey of Educator Attitude Regarding Inclusive Education within a Southern Arizona School District

Inclusive Education for students with special educational needs is a global phenomenon, a major event of momentous proportions affecting directly and indirectly a significant percentage of the world’s population. In response to international and national mandates requiring its implementation, educators everywhere are engaged in the daily task of providing educational services within inclusive general education classroom settings. It is expected that inclusion in the United States will become more prevalent in American classrooms over the next ten years due to progressively more stringent federal and state mandates. In order for inclusion to result in adequate yearly progress for all student subgroups, it is imperative that it be properly implemented. Research has established that a critical component for proper implementation is an understanding of baseline attitudes in regard to inclusive education held by educators. The purpose of this study is to explore the attitudes of pre-K-12 general and special education teachers, school site administrators, school psychologists, paraprofessionals, physical and occupational therapists, speech and language therapists, certified non-teaching, school office staff and special education office staff in a medium-sized school district in southern Arizona. This study examines attitudes held by educators, their foundations of knowledge, attitudes, perceptions and opinions that shape their attitudes; and potential recommendations for implementation strategies that are predicted to be successful by these educators.
Efeitos ergogênicos da cafeína no teste de 3.200 metros

Esta pesquisa tem como objetivo verificar os efeitos ergogenicos da cafeina em teste maximo de 3.200 metros. A amostra foi composta por 12 atletas, do sexo masculino, com idade media de 33,5 + 8 anos, estatura de 176,1 + 7,8 cm, peso de 68,9 + 8 kg e tempos de treinamento de 13 + 7,3 anos. Foram realizados 2 testes maximos de 3.200 metros. Apos o 1o teste houve um periodo de abstinencia de cafeina e no 2° houve ingestao da substância. Foi verificado que 11 dos 12 atletas obtiveram uma melhora nos tempos medios de 8,08 + 6,01seg. O coeficiente de correlacao do teste �t� pareado apresentou uma significância de p < 0,05. Concluimos que o uso da cafeina, apos uma semana de abstinencia, produz efeito ergogenico significativo na performance de atletas em teste maximo de 3.200 metros.
Cerebral Magnetic Resonance Biomarkers in Neonatal Encephalopathy: A Meta-analysis

OBJECTIVE: Accurate prediction of neurodevelopmental outcome in neonatal encephalopathy (NE) is important for clinical management and to evaluate neuroprotective therapies. We undertook a meta-analysis of the prognostic accuracy of cerebral magnetic resonance (MR) biomarkers in infants with neonatal encephalopathy. METHODS: We reviewed all studies that compared an MR biomarker performed during the neonatal period with neurodevelopmental outcome at ≥1 year. We followed standard methods recommended by the Cochrane Diagnostic Accuracy Method group and used a random-effects model for meta-analysis. Summary receiver operating characteristic curves and forest plots of each MR biomarker were calculated. χ2 tests examined heterogeneity. RESULTS: Thirty-two studies (860 infants with NE) were included in the meta-analysis. For predicting adverse outcome, conventional MRI during the neonatal period (days 1–30) had a pooled sensitivity of 91% (95% confidence interval [CI]: 87%–94%) and specificity of 51% (95% CI: 45%–58%). Late MRI (days 8–30) had higher sensitivity but lower specificity than early MRI (days 1–7). Proton MR spectroscopy deep gray matter lactate/N-acetyl aspartate (Lac/NAA) peak-area ratio (days 1–30) had 82% overall pooled sensitivity (95% CI: 74%–89%) and 95% specificity (95% CI: 88%–99%). On common study analysis, Lac/NAA had better diagnostic accuracy than conventional MRI performed at any time during neonatal period. The discriminatory powers of the posterior limb of internal capsule sign and brain-water apparent diffusion coefficient were poor. CONCLUSIONS: Deep gray matter Lac/NAA is the most accurate quantitative MR biomarker within the neonatal period for prediction of neurodevelopmental outcome after NE. Lac/NAA may be useful in early clinical management decisions and counseling parents and as a surrogate end point in clinical trials that evaluate novel neuroprotective therapies.
Performance monitor unit design for an AXI-based multi-core SoC platform

As the physical gate-count in System-On-Chip (SOC) system increases and system design complexity grows steadily, it becomes more and more difficult to achieve good resource utilization by assigning each task to certain hardware IP and tracing the execution patterns of each task efficiently. Therefore, the performance monitoring feature is getting more and more important to provide the ease of system monitoring and performance debugging. In this paper, we present a performance monitoring unit (PMU) for the AMBA Advanced eXtensible Interface (AXI) bus. The PMU has capability to measure major performance metrics, such as bus latency for the specific master requests and amount of memory traffic for specific durations. It can also measure the contention of the bus masters and slaves in the SOC. We present the distributor and the synchronization method to use multiple performance counting units as well. The performance monitoring unit has been verified in the platform FPGA board with 9 by 4 AXI interconnect configuration. These monitoring features can give the insight to system design architect by helping to find and analyze the performance bottleneck of target system.
Compensated or progressive hydrocephalus

OBJECTIVE: Raised intracranial pressure (ICP) that is associated with hydrocephalus may lead to alterations in cerebral hemodynamics and ischemic changes in the brain. In infants with hydrocephalus, defining the right moment for surgical intervention based on clinical signs alone, can sometimes be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. Furthermore, when sutures are closed. ICP does not always correlate with the size of the ventricles nor with the clinical signs or symptoms. In this study we investigated whether cerebral blood flow (CBF) can be measured by quantitative magnetic resonance angiography (MRA) in infants with progressive hydrocephalus. In addition, we investigated the relation between CBF and ICP, before and after cerebrospinal fluid (CSF) diversion. METHODS: Fifteen infants with progressive hydrocephalus (aged between 1 day and 7 months) were investigated. All patients underwent anterior fontanelle pressure (AFP) measurement, MRA and mean arterial blood pressure (MABP) measurement before and after CSF diversion. Brain volume was measured to compensate for the physiological increase of CBF during brain maturation in infants. RESULTS: The mean pre-operative ICP was 19.1 cm H20 (SD 8.4). The mean post-operative ICP was 6.7 cm H20 (SD 4.0) (p
Work Related Musculoskeletal Disorders (WMSDs)

and prevention. In the conclusion the author tries to bring these together by commenting on different methods by which these problems are considered in the United States, Canada, and the United Kingdom. For the United Kingdom reader there are problems in the second half. Although Bates worked for a considerable time in the United Kingdom at St Bartholomew's Hospital, he left more than 30 years ago. Thus his views of the process of decision making in this country are dated. For all readers the strength of the book is in his description of the importance of different phrases to describe studies, the different approaches to their interpretation by a variety of audiences, and his perception of the way in which the legislators and others react to epidemiological findings. His plea and emphasis to strengthen epidemiology is particularly welcome. The book however, does have serious weaknesses. Firstly the analysis of the policy issues and the influence of a variety of "actors" in influencing policy formulation. For example, in the field of air pollution he neglects history-for example, the National Clean Air Society, which had been active for at least 100 years, and the work done by the MRC Air Pollution Research Unit at St Bartholomew's Hospital, created before 1952. He muddles air pollution due to coal and its derivatives with that due to traffic. He neglects the importance of domestic pollution in the United Kingdom in contrast with other countries, and seems unaware of the intense involvement of the courts and lawyers in the United States in discussions on the work of the Environmental Protection Agency in the 1970s. His comments on cigarette smoking are similarly flawed. Although the Surgeon General's Report was crucial in the United States, the same cannot be said for the United Kingdom. The discussion of cigarette smoking is much shorter-and does not touch on most of the policy issues in this field. The discussion on the hazards of lead in petrol, however, epitomises a basic problem in this work. Bates does not seem to accept that there are good and bad studies. Even though bad studies may all show the same effect, that may be because the same error has been made in all of them. Part of the problem in the use of epidemiology for the determination of environmental or other risks is the need for care in design, execution, and analysis. Not all studies are equal. He is critical of the British interpretation of studies on the effect of lead in petrol. That was certainly due to the careful evaluation of those studies that had been published. These comments can be applied to all examples. Thus my recommendation is that this work should be read by those scientists involved in translating environmental risks to lay audiences. Epidemiologists and others should, however, beware of accepting the analysis and findings for the individual risk factors or policy issues. WALTERW HOLLAND
Biomedical implications of the relaxation behaviour of water related to NMR imaging

Over the past few years the applications of Nuclear Magnetic Resonance (NMR) techniques have developed along several lines as illustrated in Fig. 1. Imaging reveals tissue contrast in the whole body, isolated organs and small objects, and localises the abnormal behaviour of many soft tissues in the heterogeneous biological space. Tissue discrimination by high-resolution NMR spectroscopy helps to identify the underlying processes responsible for such abnormalities by correlating NMR relaxation times with various biological phenomena under known and well-defined conditions. The application of topical NMR provides a powerful means of obtaining metabolic details and biological information. Finally, the measurements of blood flow by NMR allow an analysis of the velocity distribution function and irregularities of blood flow in specific regions. Efforts are being made to combine proton density images of solid tissues with blood flow measurements to differentiate simultaneously the static and moving spins of wat.