Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Testing of African Americans for Susceptibility to Inherited Cancers

Abstract Identification of the genes BRCA1 and BRCA2 offers individuals at high risk for breast, ovarian, colon, or prostate cancer the opportunity to learn if they are genetically predisposed to these diseases. The department of Medicine at the University of Chicago Medical Center has a program that provides genetic testing for people with a family history of these cancers. However, African Americans do not participate in genetic testing at the same rate European Americans do. Thus, focus groups were conducted to learn more about the factors influencing the participation of African Americans in genetic testing. The findings indicated that several factors influence their participation, including perceptions about cancer survivability and lack of awareness about the role of genetic testing. The article discusses these factors and provides specific recommendations for improving African Americans' access and response to genetic testing.
Out-of-school time activity participation profiles of children with physical disabilities: a cluster analysis.

OBJECTIVE To determine out-of-school activity participation profiles of school-aged children with physical disabilities. METHODS Activity participation profiles were determined by cluster analysing 427 children's responses on multiple dimensions of participation (intensity, location, companionship, enjoyment, preference) in five activity types (recreational, active physical, social, skill-based, self-improvement). Socio-demographic, child, parent, family and environmental predictors of group membership were determined, along with child functioning, socio-demographic, self-concept and social support variables significantly associated with group membership. RESULTS The cluster analysis revealed four groups, labelled Social Participators (a highly social and neighbourhood-focused group), Broad Participators (a group of high participators who enjoy participation), Low Participators (a group with low enjoyment and weak preferences) and Recreational Participators (a group of younger children who participate in recreational activities with family members). The groups showed meaningful differences across a range of socio-demographic, child, parent, family and environmental variables. CONCLUSIONS The findings support an affective and contextual view of participation, indicating the importance of motivational theory and a person-environment approach in understanding the complexity of children's out-of-school activity participation.
Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Apicomplexans are a major lineage of parasites, including causative agents of malaria and toxoplasmosis. How such highly adapted parasites evolved from free-living ancestors is poorly understood, particularly because they contain nonphotosynthetic plastids with which they have a complex metabolic dependency. Here, we examine the origin of apicomplexan parasitism by resolving the evolutionary distribution of several key characteristics in their closest free-living relatives, photosynthetic chromerids and predatory colpodellids. Using environmental sequence data, we describe the diversity of these apicomplexan-related lineages and select five species that represent this diversity for transcriptome sequencing. Phylogenomic analysis recovered a monophyletic lineage of chromerids and colpodellids as the sister group to apicomplexans, and a complex distribution of retention versus loss for photosynthesis, plastid genomes, and plastid organelles. Reconstructing the evolution of all plastid and cytosolic metabolic pathways related to apicomplexan plastid function revealed an ancient dependency on plastid isoprenoid biosynthesis, predating the divergence of apicomplexan and dinoflagellates. Similarly, plastid genome retention is strongly linked to the retention of two genes in the plastid genome, sufB and clpC, altogether suggesting a relatively simple model for plastid retention and loss. Lastly, we examine the broader distribution of a suite of molecular characteristics previously linked to the origins of apicomplexan parasitism and find that virtually all are present in their free-living relatives. The emergence of parasitism may not be driven by acquisition of novel components, but rather by loss and modification of the existing, conserved traits.
Symptoms of communication and social impairment in toddlers with congenital heart defects.

BACKGROUND With the advances in congenital cardiac surgery and medical management, mortality rates for congenital heart defects (CHD) have declined remarkably. As the number of CHD survivors have increased there is a growing focus on developmental morbidity. The objective of the current study is to compare symptoms of communication and social impairment in 18-month-old children with different severity of CHD with those of controls. METHOD We linked prospective data from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health, with a nationwide medical CHD registry and identified 198 18-month-olds with CHD in a cohort of 47,692. Three groups of CHD were distinguished: mild/moderate (n= 122), severe (n= 54) and CHD with comorbidity (n= 22). Mothers reported on the child's communication and social skills by completing items from the Ages and Stages Questionnaire as part of the Norwegian Mother and Child Cohort Study. RESULTS Children aged 18 months old with CHD differed significantly from controls in levels of symptoms of communication impairment (P≤ 0.0001) and social impairment (P≤ 0.0001). The largest differences were found in children with CHD and comorbidity. Children with severe CHD also showed higher levels of both symptoms of communication and social impairment. Children with mild/moderate CHD showed a small difference only in symptoms of communication impairment. CONCLUSION Children with severe CHD and CHD with comorbidity show more symptoms of communication and social impairment compared with a large cohort at the age of 18 months. It is important to broaden the scope of inquiry to involve communication and social developmental domains.
Developing a Virtual Interdisciplinary Research Community in Clinical Education: Enticing People to the “Tea-Room”

Background: Many interdisciplinary collaborative research programs in the health sector are adopting the community of practice concept within virtual environments. This study explores the factors that affect the members of a geographically dispersed group of health professionals in their attempt to create an interprofessional Virtual Community of Practice (VCoP) from which to promote clinical education research.Method & Findings: A survey was used to determine participants’ degree of computer competency. System logs recorded members’ access details and site activity. Member perceptions and beliefs were established using focus groups. While members stated they were enthusiastic about the VCoP, the primary use was viewing. Their online behaviour indicated that on average it took six visits to generate a post. This suggests a stronger focus on viewing (consumption of) information than on contributing (construction of) information.Conclusions: We believe it is crucial for members to contribute during the initial phase of any pre-structured VCoP in order to overcome the consumption-construction dilemma. It is during this initial phase that members will decide on the community’s value. If the community cannot offer added value, members who engage are likely to consume for a time and then leave.
Oncolytic virotherapy in glioblastoma patients induces a tumor macrophage phenotypic shift leading to an altered glioblastoma microenvironment

Background Immunosuppressive protumoral M2 macrophages are important in pathogenesis, progression, and therapy resistance in glioblastoma (GBM) and provide a target for therapy. Recently oncolytic virotherapy in murine models was shown to change these M2 macrophages toward the pro-inflammatory and antitumoral M1 phenotype. Here we study the effects of the oncolytic virotherapy Delta24-RGD in humans, using both in vitro models and patient material. Methods Human monocyte-derived macrophages were co-cultured with Delta24-RGD-infected primary glioma stem-like cells (GSCs) and were analyzed for their immunophenotype, cytokine expression, and secretion profiles. Cerebrospinal fluid (CSF) from 18 Delta24-RGD-treated patients was analyzed for inflammatory cytokine levels, and the effects of these CSF samples on macrophage phenotype in vitro were determined. In addition, tumor macrophages in resected material from a Delta24-RGD-treated GBM patient were compared with 5 control GBM patient samples by flow cytometry. Results Human monocyte-derived M2 macrophages co-cultured with Delta24-RGD-infected GSCs shifted toward an M1-immunophenotype, coinciding with pro-inflammatory gene expression and cytokine production. This phenotypic switch was induced by the concerted effects of a change in tumor-produced soluble factors and the presence of viral particles. CSF samples from Delta24-RGD-treated GBM patients revealed cytokine levels indicative of a pro-inflammatory microenvironment. Furthermore, tumoral macrophages in a Delta24-RGD-treated patient showed significantly greater M1 characteristics than in control GBM tissue. Conclusion Together these in vitro and patient studies demonstrate that local Delta24-RGD therapy may provide a therapeutic tool to promote a prolonged shift in the protumoral M2 macrophages toward M1 in human GBM, inducing a pro-inflammatory and potentially tumor-detrimental microenvironment.
Analysis of gene–environment interactions in postnatal development of the mammalian intestine

Significance The mammalian intestine provides a key interface with several essential environmental factors, including nutrients, toxins, resident microbiota, and pathogens. Consequently, the intestine undergoes major developmental transitions that correspond to dramatic changes in the environment: one at birth and the other at weaning. These transitions reflect both developmental and environmentally induced changes in intestinal gene expression. Here, we performed a systematic analysis of global gene expression that is associated with developmental timing versus the changes that are due to the innate immune signaling pathways mediated by toll-like receptor (TLR) and IL-1 receptor families. The results reveal distinct roles of these pathways in intestinal adaptation throughout postnatal development. Unlike mammalian embryogenesis, which takes place in the relatively predictable and stable environment of the uterus, postnatal development can be affected by a multitude of highly variable environmental factors, including diet, exposure to noxious substances, and microorganisms. Microbial colonization of the intestine is thought to play a particularly important role in postnatal development of the gastrointestinal, metabolic, and immune systems. Major changes in environmental exposure occur right after birth, upon weaning, and during pubertal maturation into adulthood. These transitions include dramatic changes in intestinal contents and require appropriate adaptations to meet changes in functional demands. Here, we attempt to both characterize and provide mechanistic insights into postnatal intestinal ontogeny. We investigated changes in global intestinal gene expression through postnatal developmental transitions. We report profound alterations in small and large intestinal transcriptional programs that accompany both weaning and puberty in WT mice. Using myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) double knockout littermates, we define the role of toll-like receptors (TLRs) and interleukin (IL)-1 receptor family member signaling in postnatal gene expression programs and select ontogeny-specific phenotypes, such as vascular and smooth muscle development and neonatal epithelial and mast cell homeostasis. Metaanalysis of the effect of the microbiota on intestinal gene expression allowed for mechanistic classification of developmentally regulated genes by TLR/IL-1R (TIR) signaling and/or indigenous microbes. We find that practically every aspect of intestinal physiology is affected by postnatal transitions. Developmental timing, microbial colonization, and TIR signaling seem to play distinct and specific roles in regulation of gene-expression programs throughout postnatal development.
Evaluation of the 5-Year Survival Rate and Demographic Factors in Colorectal Cancer Patients

Background and Objective: Due to progress in treatment, the average survival rate of the colorectal cancer (CRC) patients has been steady increasing in recent decades. The aim of this study was to evaluate the survival rate and affecting demographic factors in the Iranian patients with colorectal cancer. Materials and Methods: In this retrospective study, a total of 243 cases of CRC patients, whom were referred to the registration center of Namazi Hospital in Shiraz (2003-2008), were included to the study. Collected data were analyzed by Kaplan-Meier, Log rank, and Cox regression models using the SPSS version 16 software. Results: The mean follow up time of the patients was 35.4 ±37.49 months. The overall 1-, 3-, and 5-year survival rates were estimated as 93.9, 50.3, and 27.2, respectively. The Cox regression model revealed that there were some significant correlations between the income status, initial detection method, alcohol consumption, initial treatment strategy, and metastases and the overall survival rate. Conclusion: Despite the progress in treatment, the average CRC survival rate in Iran is lower than developed countries.
Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition

Significance Enveloped viruses infect cells via fusion of viral and host cell membranes mediated by highly conserved fusion proteins. HIV-1 glycoprotein 41 (gp41) represents a family of fusion proteins with similar structures and fusion mechanisms. They couple their energetic folding to draw two membranes close for fusion, forming trimers of helical hairpins. Yet, the energy release, force generation, and kinetics associated with folding of these proteins are poorly quantified. We found that gp41 hairpins fold sequentially but in a kinetically coupled manner and that an anti-HIV drug blocked gp41 folding by a new mechanism. As major proteins on viral surfaces, fusion proteins are primary targets for vaccine development and fusion inhibitors to intervene in major infectious diseases such as AIDS, Ebola, and influenza. HIV-1 glycoprotein 41 (gp41) mediates viral entry into host cells by coupling its folding energy to membrane fusion. Gp41 folding is blocked by fusion inhibitors, including the commercial drug T20, to treat HIV/AIDS. However, gp41 folding intermediates, energy, and kinetics are poorly understood. Here, we identified the folding intermediates of a single gp41 trimer-of-hairpins and measured their associated energy and kinetics using high-resolution optical tweezers. We found that folding of gp41 hairpins was energetically independent but kinetically coupled: Each hairpin contributed a folding energy of ∼−23 kBT, but folding of one hairpin successively accelerated the folding rate of the next one by ∼20-fold. Membrane-mimicking micelles slowed down gp41 folding and reduced the stability of the six-helix bundle. However, the stability was restored by cooperative folding of the membrane-proximal external region. Surprisingly, T20 strongly inhibited gp41 folding by actively displacing the C-terminal hairpin strand in a force-dependent manner. The inhibition was abolished by a T20-resistant gp41 mutation. The energetics and kinetics of gp41 folding established by us provides a basis to understand viral membrane fusion, infection, and therapeutic intervention.
Factors influencing health-related quality of life of thalassaemic Jordanian children.

PURPOSE To assess the health-related quality of life (HRQoL) of Jordanian children with thalassaemia, identify differences in HRQoL according to socio-demographic and clinical characteristics of participants, and identify factors influencing HRQoL of thalassaemic children in Jordan. METHODS The Pediatric Quality of Life Inventory and socio-demographic and clinical data forms were used to collect data from a convenience sample of 128 thalassaemic children and 83 healthy children between the ages of 8 to 18 years. Thalassaemic children were recruited from two thalassaemia units during their blood transfusion and treatment visits. Healthy children were recruited from four public schools. RESULTS Thalassaemic children had significantly lower HRQoL mean scores in all dimensions compared with their healthy counterparts. The lowest mean scores for thalassaemic children were reported for the school functioning and the physical functioning domains (46.71 ± 21.14 and 54.19 ± 15.10), respectively. Regression analysis showed that disease complications and family history of thalassaemia explained 8.5% of the variance in the total HRQoL. CONCLUSION This study highlights the negative impact of thalassaemia on the quality of life of children, especially in terms of physical well-being and school achievement. Healthcare providers, counsellors and school teachers have very important roles in helping these children to overcome these problems and enhance their quality of life.
Sources of Stress, Coping Strategies, and Outcomes among Nursing Students during their Initial Practice

Abstract: Keywords: Sources of stress, Coping strategies, Coping outcomes, Initial clinical practice This descriptive study aimed to assess sources of stress, coping strategies, and outcomes among nursing students during their initial practice. The Lazarus stress, appraisal, and coping model was employed to guide the study. The participants of the study were 108 sophomore-nursing students studying at a government university. The tools used in the study included: 1) the Demographic Data Questionnaire, 2) the Opened End of Stress Questionnaire, 3) the Coping Strategies Questionnaire, and 4) the Anxiety Questionnaire. After completing their initial clinical practice, the participants were asked to complete all questionnaires by themselves. Data were statistically analyzed by using descriptive statistics including percentage, mean, and standard deviation. Results revealed that the students perceived stressful experiences on sources of stress, which could be categorized as follows: 1) lack of professional nursing skills; 2) lack of communication skills; 3) new environment; 4) inadequate knowledge; 5) role of clinical teachers; 6) teaching-learning methods; and 7) health problems. The confrontive coping strategy was most commonly used, followed by palliative and emotive strategies. With regard to outcomes of coping strategy use, the students felt anxiety as a moderate level. This study suggests that nursing educators need to develop strategies to help students overcome their stress during their initial clinical practice or minimize students’ sources of stress. Additionally, the availability of student counseling service, peer learners, and preceptorship may be helpful for promoting adaptive coping and decreasing anxiety.
Activation of Nuclear Factor-kappa B in Endothelial Cells of Chronic Subdural Hematoma Outer Membranes

BACKGROUND Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Nuclear factor-kappa B (NF-κB) induces the production of inflammatory cytokines and adhesion molecules, which play an essential role in angiogenesis and inflammation. Recently, the double-stranded RNA-activated protein kinase (PKR) was shown to directly interact with NF-κB subunits to influence its transcriptional activity. OBJECTIVE To examine the expression of NF-κB signaling pathway components and PKR in CSDH outer membranes. METHODS Eight patients whose outer membranes were successfully obtained during trepanation surgery were included in this study. The IκBα, IKKβ, IKKγ, NF-κB, phosphorylated ( p )-NF-κB, and PKR expression levels were examined using western blotting analysis. NF-κB expression was also examined using immunohistochemistry. We investigated whether CSDH fluid could activate NF-κB in cultured endothelial cells in Vitro. RESULTS The IκBα, IKKβ, IKKγ, and NF-κB levels were approximately the same. Additionally, p -NF-κB and PKR were detected at similar levels. Immunostaining showed that NF-κB was expressed in the vascular endothelium. p -NF-κB expression in endothelial cells was significantly induced immediately after treatment with CSDH fluid. Furthermore, NF-κB activation was significantly inhibited by treatment with antibodies directed against vascular endothelial growth factor. CONCLUSION PKR might activate NF-κB through vascular endothelial growth factor in endothelial cells, which might be associated with endothelial cell proliferation in the CSDH outer membrane. Thus, the NF-κB signaling pathway could play a critical role in CSDH growth.
A pilot study of scoliosis assessment using radiation free surface topography in children with GMFCS IV and V cerebral palsy.

BACKGROUND Prevalence of scoliosis in cerebral palsy (CP) parallels the extent of neurological impairment and causes significant morbidity. Monitoring is important but requires regular radiological investigation. Surface topography provides a non-radiological approach to scoliosis monitoring. AIM To evaluate validity, reproducibility and feasibility of Quantec(®) scans to monitor scoliosis in children with severe CP. METHODS Twenty non-ambulant children with CP, Gross Motor Function Classification System (GMFCS) grade IV/V had clinical, radiological and Quantec spinal assessment. The children were supported during scans using a seating system specifically designed for this study. Validity was assessed by comparing Quantec (Q) angle with gold standard (Cobb angle), reproducibility analysed using Bland-Altman plots and feasibility assessed using a questionnaire. RESULTS Prevalence of scoliosis on radiological examination was 65%. Of these children, 85% had curves with Cobb angle less than 28°. Quantec scanning was feasible with appropriate postural support. Mean (and standard deviation) for differences between Cobb and Quantec (Q) angle were 0.02° (6.2°) and for Quantec inter-observer variability were 0.5° (5.8°). CONCLUSIONS Quantec scanning was feasible, reproducible and had good validity when compared with Cobb angle in a supportive seating system. To consolidate these findings a further study needs to be undertaken with larger number of children with Cobb angles between 25° and 45°.