Miracle-dz/UniFAR-FTUs huggingface dataset:
Pediatric Crohn's disease: epidemiology and emerging treatment options

There has been a dramatic increase in the incidence of Crohn's disease over the last two to three decades worldwide, which has affected both the developed world and increasingly also the developing world. Crohn's disease is a disease of youth and can have a profound effect on the growing child, both in terms of growth and skeletal health as well psychosocial maturation. Environmental risk factors appear to be crucially important, but it is not clear at present whether improved hygiene, especially in childhood, influences immunological conditioning, or whether there is a direct impact on the gut from a disturbed gut microbiota. Genetic variation appears to relate to how the host interacts with its microbiota, determining susceptibility rather than causation. The outcome is a sustained immune response, clinically presenting as a relapsing/ remitting disease process. There is no current cure for Crohn's disease; treatments are designed to reduce symptoms and control inflammation, initially by inducing a remission, then trying to maintain it. Historical therapies have included 5-aminosalicylic acid-based drugs, corticosteroids, and immunomodulators. Two approaches which are gaining increasing interest are the use of exclusive enteral nutrition and biologicals. Enteral nutrition is a remarkably effective approach, though there is a limited understanding of its mechanism and difficulties in acceptance among the medical community. Biologicals are a class of drugs which specifically target molecules and pathways central to the inflammatory process; they are also very effective, but patients can develop a secondary loss of response as a result of antibodies to the biological agent. Infection and the development of secondary malignancies have provided concerns with these very potent agents and with combination therapies, but inadequately controlled disease appears to pose a bigger threat for many patients than the side effects of medications. A wide range of alternative therapies are also being explored, such as the manipulation of gut flora and pathways which might influence immune responsiveness. The marked recent increase in Crohn's disease, especially in children, has prompted a large research effort which to date has led to a better knowledge of the biology of the disease and more effective treatments. These therapies need to be used judiciously to optimize benefit and minimize side effects.
Advantages of inflatable multichannel endorectal applicator in the neo‐adjuvant treatment of patients with locally advanced rectal cancer with HDR brachytherapy

High‐dose rate endorectal brachytherapy (HDR‐EBT) is mainly used as a palliative treatment modality. In this paper, we compare dosimetry distributions for a single‐channel catheter (Miami) applicator with distributions of the inflatable multichannel (Novi Sad) endorectal applicator. The comparisons were made with respect to dose coverage to the clinical tumor volume as well as to the bladder, rectal wall, prostate, and bone marrow. Our results suggest that a multichannel applicator provides better sparing of the bone marrow by 50%, clinically uninvolved parts of the rectal wall by 70%, and bladder and prostate (in the case of male patients) by 100% in terms of ratio of median doses to critical organ volume for single‐ and multichannel endorectal applicators. Our results justify the advantage of using a multichannel endorectal brachytherapy applicator as a neo‐adjuvant treatment of patients with locally advanced rectal cancer. PACS numbers: 87.53. Jw, 87.53. Tf
A 2‐year prospective follow‐up study of temporal changes associated with post‐stroke cognitive impairment

AIMS To explore temporal patterns of change in cognitive impairments during the 2 years following stroke and to identify factors that affect these temporal changes. BACKGROUND Despite the prognostic importance, temporal changes in post-stroke cognitive impairment have not been systematically investigated. DESIGN A non-experimental, prospective, longitudinal descriptive study design. METHODS Fifty-two stroke patients were enrolled. Data were collected from April 2015 to September 2017. Cognitive function was evaluated at 5 different times (immediately, and at 3, 6, 12, and 24 months post-stroke). RESULTS Significant changes in cognitive function following stroke exhibited an "s-shaped" curve, and the most rapid changes were observed between 3 and 6 months after stroke. The incidence of post-stroke cognitive impairment ranged from 23.1% to 42.3% and was highest at 3 months and lowest at 6 months. Gender, educational level, pre-stroke cognitive and functional abilities, haematoma, and brain surgery were associated with incidence of post-stroke cognitive impairment. CONCLUSIONS The ongoing changes exhibited by patterns of cognitive impairment provide evidence that consistent efforts are required to achieve positive changes in post-stroke cognitive function. Our findings may be helpful to develop nursing care strategies aimed at improving cognitive ability and consequently the quality of life of stroke patients.
Cell Membrane Coating Nanotechnology

Nanoparticle‐based therapeutic, prevention, and detection modalities have the potential to greatly impact how diseases are diagnosed and managed in the clinic. With the wide range of nanomaterials available, the rational design of nanocarriers on an application‐specific basis has become increasingly commonplace. Here, a comprehensive overview is provided on an emerging platform: cell‐membrane‐coating nanotechnology. As a fundamental unit of biology, cells carry out a wide range of functions, including the remarkable ability to interface and interact with their surrounding environment. Instead of attempting to replicate such functions via synthetic techniques, researchers are now directly leveraging naturally derived cell membranes as a means of bestowing nanoparticles with enhanced biointerfacing capabilities. This top‐down technique is facile, highly generalizable, and has the potential to greatly augment existing nanocarriers. Further, the introduction of a natural membrane substrate onto nanoparticles surfaces has enabled additional applications beyond those traditionally associated with nanomedicine. Despite its relative youth, there exists an impressive body of literature on cell membrane coating, which is covered here in detail. Overall, there is still significant room for development, as researchers continue to refine existing workflows while finding new and exciting applications that can take advantage of this developing technology.
Neuropeptide Y1 Receptor Regulates Glucocorticoid-Induced Inhibition of Osteoblast Differentiation in Murine MC3T3-E1 Cells via ERK Signaling

High dose glucocorticoid (GC) administration impairs the viability and function of osteoblasts, thus causing osteoporosis and osteonecrosis. Neuropeptide Y1 receptor (Y1 receptor) is expressed in bone tissues and cells, and regulates bone remodeling. However, the role of Y1 receptor in glucocorticoid-induced inhibition of osteoblast differentiation remains unknown. In the present study, osteoblastic cell line MC3T3-E1 cultured in osteogenic differentiation medium was treated with or without of 10−7 M dexamethasone (Dex), Y1 receptor shRNA interference, Y1 receptor agonist [Leu31, Pro34]-NPY, and antagonist BIBP3226. Cell proliferation and apoptosis were assessed by cell counting kit-8 (CCK-8) assay and cleaved caspase expression, respectively. Osteoblast differentiation was evaluated by Alizarin Red S staining and osteogenic marker gene expressions. Protein expression was detected by Western blot analysis. Dex upregulated the expression of Y1 receptor in MC3T3-E1 cells associated with reduced osteogenic gene expressions and mineralization. Blockade of Y1 receptor by shRNA transfection and BIBP3226 significantly attenuated the inhibitory effects of Dex on osteoblastic activity. Y1 receptor signaling modulated the activation of extracellular signal-regulated kinases (ERK) as well as the expressions of osteogenic genes. Y1 receptor agonist inhibited ERK phosphorylation and osteoblast differentiation, while Y1 receptor blockade exhibited the opposite effects. Activation of ERK signaling by constitutive active mutant of MEK1 (caMEK) abolished Y1 receptor-mediated Dex inhibition of osteoblast differentiation in MC3T3-E1 cells. Taken together, Y1 receptor regulates Dex-induced inhibition of osteoblast differentiation in murine MC3T3-E1 cells via ERK signaling. This study provides a novel role of Y1 receptor in the process of GC-induced suppression in osteoblast survival and differentiation.
Diabetic and non-diabetic human cornea and tear γ-glutamyl transpeptidase activity

Background Diabetes-related eye disease is due in part to oxidative stress. Gamma-glutamyl transpeptidase (GGT) is a γ-glutamyl cycle enzyme that protects against oxidative stress via glutathione recapture. This study investigates corneal and Schirmer tears GGT activity in diabetic and non-diabetic adults aged 50 to 83 years old. Methods GGT activity was determined by colorimetric assay on 50 corneas from 14 diabetic (without keratopathy) and 20 non-diabetic donors and on Schirmer type 1 test strips (no anesthesia) of 14 diabetic and 14 non-diabetic subjects. Results Type 1 (T1) diabetic cornea GGT activity was 40% lower than Type 2 (T2) diabetic cornea GGT activity (P = 0.04), but GGT activity was similar for corneas (without keratopathy) from diabetic and non-diabetic donors (P ≥ 0.44 for all). The number of endothelial cells/unit of GGT activity in diabetic corneas was 22% higher (P = 0.1) than in non-diabetic corneas. GGT activity per Schirmer strip and GGT activity per mm of tears were 36% and 50% higher (P ≤ 0.008 for all) for non-diabetic (tear volume dependent) than diabetic donors (tear volume independent), respectively. GGT activity per mm was 50% lower in T1 than T2 diabetics (P = 0.02). Higher tear GGT activity in non-diabetic than diabetic females (P ≤ 0.05) was due to higher GGT activity in the African American females. Conclusion GGT activity was less in T1 than T2 diabetics, but comparable to non-diabetic corneas. Schirmer tear GGT activity in diabetic eyes was tear volume independent, less in T1 than T2, lower than in tear volume dependent, non-diabetic female eyes. Low cornea and tear GGT activity suggests loss of antioxidant potential and supports ocular antioxidant therapy for diabetic patients.
A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.
Prediction of Time to Crack Reinforced Concrete by Chloride Induced Corrosion

Abstract—In this paper, a review of different mathematical models which can be used as prediction tools to assess the time to crack reinforced concrete (RC) due to corrosion is investigated. This investigation leads to an experimental study to validate a selected prediction model. Most of these mathematical models depend upon the mechanical behaviors, chemical behaviors, electrochemical behaviors or geometric aspects of the RC members during a corrosion process. The experimental program is designed to verify the accuracy of a well-selected mathematical model from a rigorous literature study. Fundamentally, the experimental program exemplifies both one-dimensional chloride diffusion using RC squared slab elements of 500 mm by 500 mm and two-dimensional chloride diffusion using RC squared column elements of 225 mm by 225 mm by 500 mm. Each set consists of three water-to-cement ratios (w/c); 0.4, 0.5, 0.6 and two cover depths; 25 mm and 50 mm. 12 mm bars are used for column elements and 16 mm bars are used for slab elements. All the samples are subjected to accelerated chloride corrosion in a chloride bath of 5% (w/w) sodium chloride (NaCl) solution. Based on a prescreening of different models, it is clear that the well-selected mathematical model had included mechanical properties, chemical and electrochemical properties, nature of corrosion whether it is accelerated or natural, and the amount of porous area that rust products can accommodate before exerting expansive pressure on the surrounding concrete. The experimental results have shown that the selected model for both one-dimensional and two-dimensional chloride diffusion had ±20% and ±10% respective accuracies compared to the experimental output. The half-cell potential readings are also used to see the corrosion probability, and experimental results have shown that the mass loss is proportional to the negative half-cell potential readings that are obtained. Additionally, a statistical analysis is carried out in order to determine the most influential factor that affects the time to corrode the reinforcement in the concrete due to chloride diffusion. The factors considered for this analysis are w/c, bar diameter, and cover depth. The analysis is accomplished by using Minitab statistical software, and it showed that cover depth is the significant effect on the time to crack the concrete from chloride induced corrosion than other factors considered. Thus, the time predictions can be illustrated through the selected mathematical model as it covers a wide range of factors affecting the corrosion process, and it can be used to predetermine the durability concern of RC structures that are vulnerable to chloride exposure. And eventually, it is further concluded that cover thickness plays a vital role in durability in terms of chloride diffusion.
Multiplex Cytological Profiling Assay to Measure Diverse Cellular States

Computational methods for image-based profiling are under active development, but their success hinges on assays that can capture a wide range of phenotypes. We have developed a multiplex cytological profiling assay that “paints the cell” with as many fluorescent markers as possible without compromising our ability to extract rich, quantitative profiles in high throughput. The assay detects seven major cellular components. In a pilot screen of bioactive compounds, the assay detected a range of cellular phenotypes and it clustered compounds with similar annotated protein targets or chemical structure based on cytological profiles. The results demonstrate that the assay captures subtle patterns in the combination of morphological labels, thereby detecting the effects of chemical compounds even though their targets are not stained directly. This image-based assay provides an unbiased approach to characterize compound- and disease-associated cell states to support future probe discovery.
High Gastrointestinal Colonization Rate with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Hospitalized Patients: Emergence of Carbapenemase-Producing K. pneumoniae in Ethiopia

We investigated the gastrointestinal colonization rate and antibiotic resistance patterns of Extended-Spectrum Beta-Lactamase (ESBL)- producing Escherichia coli and Klebsiella pneumoniae in hospitalized patients admitted at Ethiopia’s largest tertiary hospital. Fecal samples/swabs from 267 patients were cultured on chrome agar. ESBL. Bacterial species identification, verification of ESBL production and antibiotic susceptibility testing were done using Vitek 2 system (bioMérieux, France). Phenotype characterization of ESBL-E.coli and ESBL- K.pneumoniae was done using Neo-Sensitabs™. ESBL positivity rate was much higher in K. pneumoniae (76%) than E. coli (45%). The overall gastrointestinal colonization rate of ESBL producing Enterobacteriaceae (ESBL-E) in hospitalized patients was 52% (95%CI; 46%–58%) of which, ESBL-E. coli and K.pneumoniae accounted for 68% and 32% respectively. Fecal ESBL-E carriage rate in neonates, children and adults was 74%, 59% and 46% respectively. Gastrointestinal colonization rate of ESBL-E.coli in neonates, children and adults was 11%, 42% and 42% respectively. Of all E. coli strains isolated from adults, children and neonates, 44%, 49% and 22% were ESBL positive (p = 0.28). The prevalence of ESBL-K.pneumoniae carriage in neonates, children and adults was 68%, 22% and 7% respectively. All K. pneumoniae isolated from neonates (100%) and 88% of K. pneumoniae isolated from children were ESBL positive, but only 50% of K.pneumoniae isolated from adults were ESBL positive (p = 0.001). Thirteen patients (5%) were carriers of both ESBL-E.coli and ESBL-KP. The overall carrier rate of ESBL producing isolates resistant to carbapenem was 2% (5/267), all detected in children; three with E.coli HL cephalosporinase (AmpC), resistant to ertapenem and two with K. pneumoniae Carbapenemase (KPC) resistant to meropenem, ertapenem and impenem. We report a high gastrointestinal colonization rate with ESBL-E and the emergence of carbapenems-resistant K. pneumoniae in Ethiopia. Urgent implementation of infection control measures, and surveillance are urgently needed to limit the spread within healthcare facilities and further to the community.
Air pollution and emergency department visits for ischemic heart disease in Montreal, Canada.

OBJECTIVES We examined the associations between emergency department (ED) visits for ischemic heart disease (IHD) and short-term elevations in ambient air pollutants (CO and NO(2)). MATERIALS AND METHODS A hierarchical clusters design was used to study ED visits (n = 4979) for ischemic heart disease (ICD-9: 410-414) that occurred at a Montreal hospital between 1997 and 2002. The generalized linear mixed models technique was applied to create Poisson models for the clustered counts of ED visits for IHD. The analysis was done by gender for two age categories, all patients and patients aged over 64 years. RESULTS The results are presented as an excess risk increase associated with the interquartile range (IQR) of daily average of the pollutant concentration. The results for NO(2) (IQR = 9.5 ppb) were 5.9% (95% CI: 2.1-9.9) for all patients and 6.2% (95% CI: 1.2-11.4) for males; for patients aged over 64: 7.1% (95% CI: 2.5-11.9) for all patients, 9.1% (95% CI: 2.8-15.7) for males, and 6.5% (95% CI: 0.7-12.7) for females (for exposure lagged by 1-day). The results for CO (IQR = 0.2 ppm): 5.4% (95% CI: 2.3-8.5) for all patients, and 7.5% (95% CI: 3.6-11.6) for males. For patients aged over 64 years, 4.9% (95% CI: 1.3-8.7) for all patients, and 7.5% (95% CI: 2.6-12.6) for males. The results show the associations for the same day exposures. CONCLUSIONS The short-term effects of nitrogen dioxide and carbon monoxide are associated significantly with daily ED visits for ischemic heart disease. For NO(2) the associations are stronger for patients aged over 64 years. As indicated by our results, it is likely that vehicular traffic, a producer of NO(2) and CO, contributes to an increased number of ED visits for IHD.
Teaching, practice, and research: an integrative approach benefiting students and faculty.

A project showing the integration of teaching, practice, and research is described. The project involved using information gathered as part of baccalaureate nursing students' assessments of women's perceptions of and responses to cesarean birth to extend a program of nursing research. Benefits to student learning and faculty research programs are identified. The project serves as a prototype for the teaching, practice, and research activities of all students and faculty in nursing and other professional disciplines.
An Agile Reverse Engineering Process based on a Framework

This paper presents an agile reverse engineering process, referred to as PARFAIT/RE, which has been abstracted from the use of a framework-based agile reengineering process, named PARFAIT. The proposition of PARFAIT/RE has been evidenced from an analysis done in a reengineering case study of a medium size system. Several factors collaborate to make PARFAIT/RE agile: a) active participation of legacy system users to validate the artifacts created and to suggest new requirements or the removal of requirements that do not belong to the business context; b) incremental approach; c) prototyping paradigm feasible from the framework instantiation; and d) use of an analysis pattern language (GRN), which was the basis for building the GREN framework. GRN belongs to the business resource management domain and supports object oriented modeling of procedural legacy systems. The analysis models created are used to support the framework instantiation.
B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction

Significance Antibody blockade of the B7-H1/PD-1 interaction induces regression of advanced human cancers in some patients, while recurrence occurs in others due to tumor escape from T cell attack. Here, we describe a possible mechanism of tumor escape from therapy caused by biased stimulation of T cells to dominant antigen. Based on this finding, we tested a split immunization approach to prevent cancer recurrence in mouse tumor models. These findings may help design approaches for combination cancer immunotherapies. Induced B7-H1 expression in the tumor microenvironment initiates adaptive resistance, which impairs immune functions and leads to tumor escape from immune destruction. Antibody blockade of the B7-H1/PD-1 interaction overcomes adaptive resistance, leading to regression of advanced human cancers and survival benefits in a significant fraction of patients. In addition to cancer cells, B7-H1 is expressed on dendritic cells (DCs), but its role in DC functions is less understood. DCs can present multiple antigens (Ags) to stimulate dominant or subdominant T cell responses. Here, we show that immunization with multiple tumor Ag-loaded DCs, in the absence of B7-H1, vastly enhances cytotoxic T lymphocyte (CTL) responses to dominant Ag. In sharp contrast, CTL responses to subdominant Ag were paradoxically suppressed, facilitating outgrowth of tumor variants carrying only subdominant Ag. Suppressed CTL responses to subdominant Ag are largely due to the loss of B7-H1–mediated protection of DCs from the lysis of CTL against dominant Ag. Therefore, B7-H1 expression on DCs may help maintain the diversity of CTL responses to multiple tumor Ags. Interestingly, a split immunization approach, which presents dominant and subdominant Ags with different DCs, promoted CTL responses to all Ags and prevented tumor escape in murine tumor models. These findings have implications for the design of future combination cancer immunotherapies.