Miracle-dz/UniFAR-FTUs huggingface dataset:
The Logic Model in Action against Tobacco Use: A Case Study

Mississippi, an early player in tobacco prevention efforts, used a logic model based in CDC's Best Practices that had seven levels: inputs (community leaders, statewide partners, state Health Department, Attorney General's office), activities (cessation, chronic disease, media/marketing, youth programs, school programs, community/state programs, law enforcement), outputs (nicotine cessation and treatment programs, exposure to no-tobacco, pro-health media and other programs, smoking bans, ordinances, and policies), initial outcomes (awareness of programs, changes in youth knowledge and attitudes, increased enforcement efforts), intermediate outcomes (increased program utilization, reduced youth initiation of tobacco use, improved community culture regarding tobacco), long-term outcomes (reduced youth tobacco use, reduced exposure to secondhand smoke), and impact (reduced tobacco-related sickness and death). With enough simplicity to be clear, enough detail to offer guidance, and sufficient grounding in CDC's Best Practices to provide a persuasive rationale for each component, the present logic model had immediate applications and helped with program evaluation.
Automatic document orientation detection and categorization through document vectorization

This paper presents an automatic orientation detection and categorization technique that is capable of detecting the orientation of multilingual documents with arbitrary skew and categorizing document images according to the underlying languages. We carry out orientation detection and categorization through document vectorization, which encodes document orientation and language information and converts each document image into an electronic document vector through the exploitation of the density and distribution of vertical component runs. For each language of interest, a pair of vector templates is first constructed through a training process. Orientation and category of the query image are then determined based on distances between the query document vector and the constructed vector templates. Experiments over 492 testing document images show that the average orientation detection and categorization rates reach up to 97.56% and 99.59%, respectively.
RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression

Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry. Highlighted article: RING1 proteins, which are essential components of Polycomb repressive complex-1, control proximal-distal patterning of the mouse forelimb by integrating developmental signals to regulate MEIS expression.
Zur Zukunft von Cannabis als Medizin

Die Verwendung von naturlichem Marihuana als Medizin wird Bestand haben. Sowohl seine Sicherheit als auch seine Wirksamkeit sind durch viele anekdotische und klinische Erfahrungen gut nachgewiesen. Pharmazeutische Cannabinoid-Praparate werden entwickelt werden, einige davon werden erfolgreich mit dem de facto Goldstandard, legal erhaltlichem naturlichem Marihuana konkurrieren. Stichworter: Marihuana, medizinische Verwendung, Cannabis
Bureaucratic control mechanisms and the implementation of quality improvement programmes in home health agencies

This paper examines the relationship between structural characteristics of home health agencies and the adoption of continuous quality improvement (CQI) technology. Home health services are the fastest growing component of the US healthcare system. Concerns regarding quality management derive from the remote service delivery modality and the heavy reliance on paraprofessional staff. Results of a survey of 361 agency directors indicate that, in contrast to observations in the hospital industry, the implementation of CQI in home healthcare is facilitated by increased formalisation and standardisation of work processes. These bureaucratic mechanisms may provide requisite structural integrity for adoption of inherently decentralising CQI programmes.
Guidelines for Early Identification, Screening, and Clinical Management of Children With Autism Spectrum Disorders

Congratulations to the American Academy of Pediatrics (AAP). Two of their recent clinical reports published in Pediatrics , “Identification and Evaluation of Children With Autism Spectrum Disorders”1 and “Management of Children With Autism Spectrum Disorders,”2 will enable pediatricians to address parent concerns sooner, facilitating the early identification of children with autism spectrum disorders (ASDs). As physicians and developmentalists with decades of accumulated experience in working with children with developmental challenges, we applaud and welcome these publications. However, we would like to expand on these reports. In this commentary we (1) describe a broader functional/developmental framework for screening for ASDs, (2) provide a critique of the current trend toward behavioral treatments as primary intervention strategies, and (3) present research evidence for functional/developmental approaches. A broader and more refined “functional” developmental framework3 looks for compromises in the child's healthy milestones and helps parents and other caregivers work with the child to improve that area of functioning and overall healthy progression. * This approach helps families identify challenges early in the first and second years of life and to begin to help their children before the 18- and 24-month screenings recommended by the AAP.4 An overfocus on specific problem behaviors without a framework for promoting healthy development may prove to be counterproductive.5 Screening that focuses on specific behaviors or symptoms (eg, whether a child responds to his or her name toward the end of the first year) may identify a percentage … Address correspondence to Stanley I. Greenspan, MD, 7201 Glenbrook Road, Bethesda, MD 20814. E-mail: stanleygreenspan{at}gmail.com
WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate

Neural crest (NC) cells arise early in vertebrate development, migrate extensively and contribute to a diverse array of ectodermal and mesenchymal derivatives. Previous models of NC formation suggested derivation from neuralized ectoderm, via meso-ectodermal, or neural-non-neural ectoderm interactions. Recent studies using bird and amphibian embryos suggest an earlier origin of NC, independent of neural and mesodermal tissues. Here, we set out to generate a model in which to decipher signaling and tissue interactions involved in human NC induction. Our novel human embryonic stem cell (ESC)-based model yields high proportions of multipotent NC cells (expressing SOX10, PAX7 and TFAP2A) in 5 days. We demonstrate a crucial role for WNT/β-catenin signaling in launching NC development, while blocking placodal and surface ectoderm fates. We provide evidence of the delicate temporal effects of BMP and FGF signaling, and find that NC development is separable from neural and/or mesodermal contributions. We further substantiate the notion of a neural-independent origin of NC through PAX6 expression and knockdown studies. Finally, we identify a novel pre-neural border state characterized by early WNT/β-catenin signaling targets that displays distinct responses to BMP and FGF signaling from the traditional neural border genes. In summary, our work provides a fast and efficient protocol for human NC differentiation under signaling constraints similar to those identified in vivo in model organisms, and strengthens a framework for neural crest ontogeny that is separable from neural and mesodermal fates. Highlighted article: A new protocol for human neural crest induction from hESCs is fast and efficient, and involves TGFβ, FGF and BMP signaling to specify the neural crest independent of neural ectoderm and mesoderm.
GATA4 regulates Fgf16 to promote heart repair after injury

Although the mammalian heart can regenerate during the neonatal stage, this endogenous regenerative capacity is lost with age. Importantly, replication of cardiomyocytes has been found to be the key mechanism responsible for neonatal cardiac regeneration. Unraveling the transcriptional regulatory network for inducing cardiomyocyte replication will, therefore, be crucial for the development of novel therapies to drive cardiac repair after injury. Here, we investigated whether the key cardiac transcription factor GATA4 is required for neonatal mouse heart regeneration. Using the neonatal mouse heart cryoinjury and apical resection models with an inducible loss of GATA4 specifically in cardiomyocytes, we found severely depressed ventricular function in the Gata4-ablated mice (mutant) after injury. This was accompanied by reduced cardiomyocyte replication. In addition, the mutant hearts displayed impaired coronary angiogenesis and increased hypertrophy and fibrosis after injury. Mechanistically, we found that the paracrine factor FGF16 was significantly reduced in the mutant hearts after injury compared with littermate controls and was directly regulated by GATA4. Cardiac-specific overexpression of FGF16 via adeno-associated virus subtype 9 (AAV9) in the mutant hearts partially rescued the cryoinjury-induced cardiac hypertrophy, promoted cardiomyocyte replication and improved heart function after injury. Altogether, our data demonstrate that GATA4 is required for neonatal heart regeneration through regulation of Fgf16, suggesting that paracrine factors could be of potential use in promoting myocardial repair. Highlighted article: GATA4 and FGF16 are important mediators of cardiomyocyte proliferation and hypertrophy during neonatal heart repair following cryoinjury and apex resection.
The variation in treating colorectal cancer between Europe and America

177 ISSN 1758-194X 10.2217/CRC.13. 25 © 2013 Future Medicine Ltd Colorect. Cancer (2013) 2(3), 177–180 1Radioterapia Oncologica, Universita Campus Bio-Medico, Rome, Italy 2Oncologia Medica, Universita Campus Bio-Medico, Rome, Italy *Author for correspondence: f.cellini@unicampus.it Colorectal cancer epidemiology in Europe & the USA Colorectal cancer (CRC) represents the fourth most common cancer in the USA and the second most common in Europe. In 2012, 103,170 new estimated cases were diagnosed in the USA, with 51,690 deaths. In Europe, 412,000 cases were diagnosed, with 217,000 deaths [1]. Rectal cancer tumors in particular (i.e., a lesion with distal extension up to ≤15 cm from the anal margin) are less fre­ quent, but still account for 35% of CRCs, with an incidence of 15–25/100,000 per year in Europe, and for just under 40,000 newly diagnosed cases in the USA between 2010 and 2011, with a different natural disease course, type of relapse and recur­ rence after treatment with respect to colon tumors [2,3]. Despite these data, the incidence and mortality of CRC has decreased in the last decade, possibly because of earlier diagnosis and improvement in treatment modalities. On a worldwide scale, a better definition of the standards of care contrib­ uted to the global amelioration of clinical results. However, some controversies still remain and some differences between the approaches used in the USA and Europe are quite important.
Immune responses in a community with a high incidence of tuberculosis

Prepubertal immunisation to reduce heterosexual spread of subtype C of HIV -1 is one of the objectives of the HIV/AIDS vaccine initiative in South Africa. A potential threat to this goal is the possibility that vaccine efficacy could be impaired by sustained or intermittent immune activation caused by endemic worm infestation. The results of surveys that were undertaken to determine the prevalence of helminthic infection in children and adolescents at schools in Ravensmead and Uitsig, which are adjacent residential areas in Cape Town, South Africa, are relevant in this context. The overall prevalence of ascariasis and/or trichuriasis, with the standard error bracketed, was 55.4 (0.8) % (n = 3 890). The range was from 43.1 (2.1) % in children who were 6 years old (n = 541) to 59.9 (3.3) % in adolescents aged 14 or more (n = 217). In addition to Ascaris and Trichuris, 2.2 (0.23) % of children had eggs of the dwarf tapeworm (Hymenolepis nana) in their faeces. These substantial infection rates were in an age group intended as a primary target for vaccination against HIV/AIDS in communities that are not the poorest of the poor, and which have been well-serviced for many years in terms of public health, medical, educational and other facilities. The socioeconomic and demographic conditions in the two communities have not changed over time and the population density is intermediate between that in slums and affluent suburbs. Where poverty is worse, such as in slums in Cape Town and Durban, the prevalence and intensity of worm infestation are known to increase, as does the incidence of HIV/AIDS as well as enteric and respiratory diseases. Development and testing of vaccines against HIVand the medical management of AIDS are costly and difficult for various reasons, whereas control of worm infestation is inexpensive, achievable and could yield spinoffs beyond currently-known benefits.
Epb41l5 competes with Delta as a substrate for Mib1 to coordinate specification and differentiation of neurons

We identified Erythrocyte membrane protein band 4.1-like 5 (Epb41l5) as a substrate for the E3 ubiquitin ligase Mind bomb 1 (Mib1), which is essential for activation of Notch signaling. Although loss of Epb41l5 does not significantly alter the pattern of neural progenitor cells (NPCs) specified as neurons at the neural plate stage, it delays their delamination and differentiation after neurulation when NPCs normally acquire organized apical junctional complexes (AJCs) in the zebrafish hindbrain. Delays in differentiation are reduced by knocking down N-cadherin, a manipulation expected to help destabilize adherens junctions (AJs). This suggested that delays in neuronal differentiation in epb41l5-deficient embryos are related to a previously described role for Epb41l5 in facilitating disassembly of cadherin-dependent AJCs. Mib1 ubiquitylates Epb41l5 to promote its degradation. DeltaD can compete with Epb41l5 to reduce Mib1-dependent Epb41l5 degradation. In this context, increasing the number of NPCs specified to become neurons, i.e. cells expressing high levels of DeltaD, stabilizes Epb41l5 in the embryo. Together, these observations suggest that relatively high levels of Delta stabilize Epb41l5 in NPCs specified as neurons. This, we suggest, helps coordinate NPC specification with Epb41l5-dependent delamination and differentiation as neurons. Highlighted article: The FERM domain protein Epb41l5 competes with the Notch ligand Delta as a substrate for Mib1 E3 ligase to coordinate neuronal specification and differentiation at the post-translational level.
Functional and Physiological Determinants of Perceived Disability in Individuals Diagnosed with Osteoarthritis of the Hip

Objectives: The main objective of this pilot study was to investigate which standardized functional and physiological test best predicted perceived disability in a single group of 21 individuals diagnosed with osteoarthritis of the hip. Design: Men and women between 60 and 70 years old with osteoarthritis of the hip were selected. If participants passed study criteria, the Western Ontario McMaster University questionnaire (WOMAC), 6 Minute Walk Test (6MWT) and Timed up and Go (TUG), strength testing and aerobic testing were obtained in one single assessment. Results: Regression analysis revealed that wait time, hip abduction strength of the affected side, Aerobic Capacity (VO 2 Peak), hip Extension Peak Torque, hip Flexion Peak Torque, TUG and 6MWT were significantly correlated with the WOMAC. Yet, the 6MWT had the highest significant correlation (r = -0.86, p ≤ 0.0001); R2 = 0.75 or 75% with the WOMAC total scores, (r = -0.82, p ≤ 0.0001); R2 = 0.67 or 67% with the WOMAC function and (r = -0.60, p = .002); R2 = 0.36 or 36% with the WOMAC stiffness. While the VO 2 Peak revealed the highest significant correlation (r = 0.76, p ≤ .0001); R2 = 0.57 or 57% with the WOMAC pain. Conclusions: The 6MWT and the VO 2 Peak seem to be essential functional and physiological assessment tools to determine perceived disability in individuals with hip OA. The perceived disability may provide new or comprehensive knowledge of the disability problems experienced by individuals with osteoarthritis of the hip, and the association of patient perception with objective measures of functional and physiological capacity might strengthen the clinical value of this knowledge.
MicroRNAs in neural development: from master regulators to fine-tuners

The proper formation and function of neuronal networks is required for cognition and behavior. Indeed, pathophysiological states that disrupt neuronal networks can lead to neurodevelopmental disorders such as autism, schizophrenia or intellectual disability. It is well-established that transcriptional programs play major roles in neural circuit development. However, in recent years, post-transcriptional control of gene expression has emerged as an additional, and probably equally important, regulatory layer. In particular, it has been shown that microRNAs (miRNAs), an abundant class of small regulatory RNAs, can regulate neuronal circuit development, maturation and function by controlling, for example, local mRNA translation. It is also becoming clear that miRNAs are frequently dysregulated in neurodevelopmental disorders, suggesting a role for miRNAs in the etiology and/or maintenance of neurological disease states. Here, we provide an overview of the most prominent regulatory miRNAs that control neural development, highlighting how they act as ‘master regulators’ or ‘fine-tuners’ of gene expression, depending on context, to influence processes such as cell fate determination, cell migration, neuronal polarization and synapse formation. Summary: This Review summarizes the main functions of microRNAs in several aspects of neural development, including neurogenesis, migration, axon and dendrite development, and synaptic plasticity.
SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development

Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the human NOTCH1 and zebrafish notch1b genes. These enhancers were able to direct arterial endothelial cell-restricted expression in transgenic models. Genetic disruption of SoxF binding sites established a clear requirement for members of this group of transcription factors (SOX7, SOX17 and SOX18) to drive the activity of these enhancers in vivo. Endogenous deletion of the notch1b enhancer led to a significant loss of arterial connections to the dorsal aorta in Notch pathway-deficient zebrafish. Loss of SoxF function revealed that these factors are necessary for NOTCH1 and notch1b enhancer activity and for correct endogenous transcription of these genes. These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates. Summary: Identification of novel enhancers in vertebrate Notch1 genes places SoxF transcription factors directly upstream of Notch signalling in controlling arterial specification and differentiation.
Synergism between canoe and scribble mutations causes tumor-like overgrowth via Ras activation in neural stem cells and epithelia

Over the past decade an intriguing connection between asymmetric cell division, stem cells and tumorigenesis has emerged. Neuroblasts, which are the neural stem cells of the Drosophila central nervous system, divide asymmetrically and constitute an excellent paradigm for investigating this connection further. Here we show that the simultaneous loss of the asymmetric cell division regulators Canoe (afadin in mammals) and Scribble in neuroblast clones leads to tumor-like overgrowth through both a severe disruption of the asymmetric cell division process and canoe loss-mediated Ras-PI3K-Akt activation. Moreover, canoe loss also interacts synergistically with scribble loss to promote overgrowth in epithelial tissues, here just by activating the Ras-Raf-MAPK pathway. discs large 1 and lethal (2) giant larvae, which are functionally related to scribble, contribute to repress the Ras-MAPK signaling cascade in epithelia. Hence, our work uncovers novel cooperative interactions between all these well-conserved tumor suppressors that ensure tight regulation of the Ras signaling pathway. Summary: In Drosophila, simultaneous loss of Cno and Scrib results in disrupted asymmetric cell division and Ras-PI3K-Akt activation in neuroblasts, and in ectopic Ras-MAPK signaling in epithelia.
The matrix protein Tiggrin regulates plasmatocyte maturation in Drosophila larva

The lymph gland (LG) is a major source of hematopoiesis during Drosophila development. In this tissue, prohemocytes differentiate into multiple lineages, including macrophage-like plasmatocytes, which comprise the vast majority of mature hemocytes. Previous studies have uncovered genetic pathways that regulate prohemocyte maintenance and some cell fate choices between hemocyte lineages. However, less is known about how the plasmatocyte pool of the LG is established and matures. Here, we report that Tiggrin, a matrix protein expressed in the LG, is a specific regulator of plasmatocyte maturation. Tiggrin mutants exhibit precocious maturation of plasmatocytes, whereas Tiggrin overexpression blocks this process, resulting in a buildup of intermediate progenitors (IPs) expressing prohemocyte and hemocyte markers. These IPs likely represent a transitory state in prohemocyte to plasmatocyte differentiation. We also found that overexpression of Wee1 kinase, which slows G2/M progression, results in a phenotype similar to Tiggrin overexpression, whereas String/Cdc25 expression phenocopies Tiggrin mutants. Further analysis revealed that Wee1 inhibits plasmatocyte maturation through upregulation of Tiggrin transcription. Our results elucidate connections between the extracellular matrix and cell cycle regulators in the regulation of hematopoiesis. Summary: The matrix protein Tiggrin, which is modulated by cell cycle regulators, inhibits the maturation of plasmatocytes in the Drosophila larval lymph gland through an integrin-independent mechanism.