Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-21 as a therapeutic target in inflammatory disorders

Introduction: IL-21, a cytokine produced by activated CD4+ cells, activated natural killer T cells and T helper cells in the germinal centers, is involved in the control of the function of both immune and parenchymal cells. Areas covered: IL-21 is overproduced in many chronic inflammatory disorders, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, type I diabetes and systemic lupus erythematosus, and studies in experimental models indicate that IL-21 plays an important role in sustaining tissue-damaging immune responses in such pathologies. However, genetic deficiency of IL-21 associates with inflammatory bowel diseases and blockade of IL-21 in the early phases exacerbates the disease progression in some models of rheumatoid arthritis and systemic lupus erythematosus, thus suggesting a dual role of IL-21 in the control of immune-mediated diseases. IL-21 can exert additional protective functions for the host as it promotes cytotoxic responses against tumors and viruses. Expert opinion: We here review the available data on the role of IL-21 in chronic inflammatory diseases and discuss the therapeutic benefit of IL-21 inhibitors in such diseases as well as the potential risks of such treatments.
Genomic Boundaries between Human Populations

Different authors disagree on whether human genome variation should be described as continuous or discontinuous; in the latter case, by attributing an individual’s genotype to one genetic cluster, one would also obtain information on the individual’s genome in general. An analysis of 377 microsatellites of the CEPH human diversity panel was interpreted as evidence that most genotypes cluster into one of five distinct groups, approximately corresponding to continents, which were pro- posed by some authors as the major biological subdivisions of humankind. Here we analyse the same dataset by a specific numerical method, designed to detect genomic boundaries, i.e. zones of increased change in maps of genomic variation. We show that statistically significant boundaries can be described between groups of populations, but different clusters are identified, depending on the assumptions of the model. In addition, these clusters do not correspond to the clusters inferred from previous analyses of the same or of other polymorphisms. We conclude that it is indeed possible to cluster genotypes according to geography, but no study so far identified unambiguously anything that can be regarded as a major genetic subdivision of humankind, and hence discontinuous models of human diversity are unsupported by data.
Evidence-based clinical practice guidelines on management of pain in older people.

Pain in older people is not only under-recognised, but is also under-treated. Many professional bodies have documented that pain in this rapidly growing population is poorly controlled [1–7]. This may be related to attitudes and beliefs held by older people, which in turn affects their reporting of pain [8] but also due to misconceptions and educational deficits by health professionals [9, 10]. Treatment when prescribed is often limited to basic medication seldom tailored to the individual [11–14]. There is also a general failure by professionals to consider alternative pain relief options [2]. No doubt more needs to done and national guidance on the management of pain in older people is long overdue. Older people are different; the bio-physiological changes that occur with ageing, the accumulation of co-morbidities and co-prescription of medication, frailty and psychosocial changes make older people rather unique when considering treatment modalities for pain control. The British Geriatric Society and British Pain Society have collaborated to produce the first UK guideline on the management of pain in older people. The recommendations follow an extensive systematic review of the available literature and will help health professionals consider the options available when managing pain in older patients. The guideline has been categorised into sections dealing with pharmacology, interventional therapies, psychological interventions, physical activity and assistive devices and complementary therapies. This article provides a summary of the recommendations. The full guideline is available in the supplement accompanying this issue of the journal.
Oral and dental diseases in a population of domestic ferrets (Mustela putorius furo).

OBJECTIVE Domestic ferrets have been used for many purposes, but recently their popularity as companion animals has increased greatly. However, data on their oral and dental diseases are rare. The objective of this study was therefore to describe oral and dental diseases in a population of client-owned domestic ferrets. METHODS In this cross-sectional clinical study, detailed oral and dental examination and full-mouth dental radiographs were performed in 57 client-owned ferrets. RESULTS Variations in occlusion and number of roots per tooth were noted in comparison with previously published literature on ferrets. Periodontal disease, attrition/abrasion and dental fractures, especially of the canine teeth, were commonly observed. Periapical disease associated with dental fractures, malocclusion, tooth resorption and neoplasia was uncommon. CONCLUSION AND CLINICAL RELEVANCE This study indicates that thorough oral and dental examination supported by dental radiography under general anaesthesia should be performed in domestic ferrets as a part of regular veterinary care.
The Influence of Cognitive Reserve on Strategy Selection in Normal Aging

Abstract Cognitive reserve (CR) has been proposed as a latent variable that can account for the frequent discrepancy between an individual's underlying level of brain pathology and their observed clinical outcome. A possible behavioral manifestation of CR is best strategy choice. Older adults have been shown to choose sub-optimal strategies for performing various tasks. The present study attempted to investigate whether greater levels of CR could predict greater strategy selection, particularly in older adults. A computational estimation task was administered to 20 healthy young adults (mean age = 24.7 ± 3.6; 20–31 years) and 18 healthy older adults (68.2 ± 4.5; 62–77 years) wherein participants needed to estimate the product of two two-digit numbers by using one of two strategies. The results revealed an effect of age group on strategy choice and supported the hypothesis that CR is associated with increased strategy selection abilities. (JINS, 2013, 19, 1–4)
Are Heart Disease Patients More Likely to have Healthy Lifestyle Behaviors? Results from the 2000 Behavioral Risk Factor Surveillance Survey

Background Our objective was to determine whether persons with coronary heart disease (CHD) were more likely to engage in healthy lifestyle behaviors (HLBs) than persons without CHD. Design Cross-sectional study. Methods Data from the 2000 Behavioral Risk Factor Surveillance System (BRFSS) (n = 35 677) were analyzed. HLBs included maintaining an ideal body weight (body mass index < 25.0), eating five or more fruits and vegetables daily, performing at least 30 minutes of leisure time physical activity (LTPA) at least five times per week and non-smokers (former and never smokers). Logistic regression was used to determine whether persons with CHD were more likely to engage in all four HLBs than persons without CHD after adjusting for age, sex, race and education. Results Only 6.3% of persons with CHD and 6.8% among persons without CHD engaged in all four HLBs. In the crude analysis, persons with CHD were 10% less likely than persons without CHD to engage in all four HLBs [odds ratio (OR) = 0.9; 95% confidence interval (CI) = 0.7-1.3]. After adjusting for covariates, persons with CHD were equally as likely to engage in all four HLBs as persons without CHD (OR = 1.0; 95% CI = 0.7-1.3). Conclusions Overall, only a small proportion of persons engaged in all four HLBs. After adjusting for covariates, persons with CHD were just as likely as persons without CHD to engage in all four HLBs. Additional efforts are needed to increase the proportion of adults engaging in all four HLBs, particularly among persons with CHD. J Cardiovasc Risk 10:207-212 © 2003 Lippincott Williams & Wilkins.
Performance status assessment in cancer patients

Performance status assessment, Karnofsky performance status (KPS), and Eastern Cooperative Oncology Group (ECOG) scales were performed in 100 consecutive patients independently by two physicians and by the patients themselves to evaluate the scales' validity and reliability. Findings of Kendall's correlation were highly significant between physicians (0.76 for KPS, 0.75 for ECOG) and between physicians and patients (0.65 for KPS, 0.59 for ECOG). The authors point out that patients' self evaluation could provide a valuable and reliable assessment.
AG 490 inhibits G 1S traverse in BALB / c-3 T 3 cells following either mitogenic stimulation or exogenous expression of E 2 F-1

AG490, a member of the tryphostin family of protein kinase inhibitors, repressed G0-G1 traverse in BALB/c-3T3 cells. While the early induction of STAT activity was repressed by AG490, extracellular signal-regulated kinase (ERK) activation was unaffected and a pattern of gene expression suggested that cells exited G0 in the presence of the inhibitor. Although AG490 did not alter the induction of cyclin D1 protein, neither cyclin D1nor cyclin D3-associated kinase activity was observed in growth-inhibited cells. Surprisingly, p130 was partially phosphorylated, and E2F3A protein was expressed in mitogen-stimulated AG490-treated cells despite the lack of cyclin D-associated kinase activity. These data suggest that AG490 inhibits a cellular pathway required for mid-G0-G1 traverse that is located after the induction of early processes potentially mediated by E2F (although independent of cyclin D-associated kinase activity) but before the late G1 increase in E2F-dependent transcription. Infection of AG490-treated cells with an E2F-1 adenovirus caused the induction of cyclin A, but could not overcome the drug-induced cell cycle arrest that was coincident with the repression of cyclin-dependent kinase 2 (cdk2)-associated kinase activation. We conclude that cdk2-associated kinase activity is modulated by a cellular process repressed by AG490. Furthermore, this cdk2associated kinase activity is required for G0-G1 traverse in some role other than the regulation of E2F-dependent transcription. [Mol Cancer Ther. 2004;3(2):205–213]
The impact of light, noise, cage cleaning and in-house transport on welfare and stress of laboratory rats

Human interaction and physical environmental factors are part of the stimuli presented to laboratory animals everyday, influencing their behaviour and physiology and contributing to their welfare. Certain environmental conditions and routine procedures in the animal facility might induce stress responses and when the animal is unable to maintain its homeostasis in the presence of a particular stressor, the animal's wellbeing is threatened. This review article summarizes several published studies on the impact of environmental factors such as light, noise, cage cleaning and in-house transport on welfare and stress of laboratory rats. The behaviour and physiological responses of laboratory rats to different environmental housing conditions and routine procedures are reviewed. Recommendations on the welfare of laboratory rats and refinements in experimental design are discussed and how these can influence and improve the quality of scientific data.
A fast unblocking scheme for distance protection to identify symmetrical fault occurring during power swings

It is demonstrated in this paper that the change rate of the sum of three-phase active powers and reactive power are the cosine function and the sinusoidal function with respect to the phase difference between the two power systems during power swings. In this case, they cannot be lower than the threshold of 0.7 after they are normalized. However, they level off to 0 when a three-phase fault occurs during power swings. Based on this analysis, a cross-blocking scheme to rapidly identify the symmetrical fault occurring during the power swings is therefore proposed. By virtue of the improved two-instantaneous-value-product algorithm, the calculation of the active and reactive power is immune to the variation of the system power frequency. As the integration based criterion, this criterion has high stability. Simulation results show that this scheme is of high reliability and fast time response. The longest time delay is up to 30 ms
Delayed Breast Implant Reconstruction: Is Radiation Therapy Associated With Capsular Contracture or Reoperations?

We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during the period between 1999 and 2006. A history of radiation therapy was associated with increased risk of severe capsular contracture for 1- and 2-stage procedures, with adjusted hazard ratios (HR) of 3.3 (95% confidence interval [CI]: 0.9–12.4) and 7.2 (95% CI: 2.4–21.4), respectively. Similarly, a history of radiation therapy was associated with a non-significantly increased risk of reoperation after both 1-stage (HR = 1.4; 95% CI: 0.7–2.5) and 2-stage (HR = 1.6; 95% CI: 0.9–3.1) procedures. Reconstruction failure was highest (13.2%) in the 2-stage procedures with a history of radiation therapy. Breast reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy.
Mutations in the X-linked Intellectual Disability Gene, zDHHC9, Alter Autopalmitoylation Activity by Distinct Mechanisms*

Background: Two alleles of the mammalian Ras protein acyltransferase are associated with X-linked intellectual disabilities. Results: Mutations of zDHHC9 isolated from XLID patients result in defects to steady state autopalmitoylation levels. Conclusion: Although the zDHHC9 mutations produce similar phenotypes, they are guided by distinct mechanisms. Significance: Elucidation of the catalytic mechanism of PATs is a critical step in designing pharmacological interventions. Early onset intellectual disabilities result in significant societal and economic costs and affect 1–3% of the population. The underlying genetic determinants are beginning to emerge and are interpreted in the context of years of work characterizing postsynaptic receptor and signaling functions of learning and memory. DNA sequence analysis of intellectual disability patients has revealed greater than 80 loci on the X-chromosome that are potentially linked to disease. One of the loci is zDHHC9, a gene encoding a Ras protein acyltransferase. Protein palmitoylation is a reversible modification that controls the subcellular localization and distribution of membrane receptors, scaffolds, and signaling proteins required for neuronal plasticity. Palmitoylation occurs in two steps. In the first step, autopalmitoylation, an enzyme-palmitoyl intermediate is formed. During the second step, the palmitoyl moiety is transferred to a protein substrate, or if no substrate is available, hydrolysis of the thioester linkage produces the enzyme and free palmitate. In this study, we demonstrate that two naturally occurring variants of zDHHC9, encoding R148W and P150S, affect the autopalmitoylation step of the reaction by lowering the steady state amount of the palmitoyl-zDHHC9 intermediate.
Critical role of Brg1 member of the SWI/SNF chromatin remodeling complex during neurogenesis and neural crest induction in zebrafish

Brg1 is a member of the SWI/SNF chromatin‐remodeling complex, and in some organisms Brg1 has been shown to interact with β‐catenin and positively control the TCF/LEF transcription factor that is located downstream of the Wnt signal transduction pathway. During development, TCF/LEF activity is critical during neurogenesis and head induction. In zebrafish, Brg1‐deficient embryos exhibit retinal cell differentiation and eye defects; however, the role of Brg1 in neurogenesis and neural crest cell induction remains elusive. We used zebrafish deficient in Brg1 (yng) or Brg1 specific‐morpholino oligonucleotide‐mediated knockdown to analyze the embryonic requirements of Brg1. Our results indicate that reduction in Brg1 expression leads to the expansion of the forebrain‐specific transcription factor, six3, and marked reduction in expression of the mid/hind‐brain boundary and hind‐brain genes, engrailed2 and krox20, respectively. At 12 hpf, the expression of neural crest specifiers are severely affected in Brg1‐morpholino‐injected embryos. These results suggest that Brg1 is involved in neural crest induction, which is critical for the development of neurons, glia, pigment cells, and craniofacial structures. Brg1 is a maternal factor, and brg1‐deficient embryos bearing the yng mutation derived from heterozygote intercrosses exhibit lesser effects on neural crest–specific gene expression, but show defects in neurogenesis and neural crest cell differentiation. This is exhibited by the aberrant brain patterning, a reduction in the sensory neurons, and craniofacial defects. These results further elucidate the critical role for Brg1 in neurogenesis, neural crest induction, and differentiation. Developmental Dynamics 235:2722–2735, 2006. © 2006 Wiley‐Liss, Inc.
Contribution of cattle products to dietary intake of trace and toxic elements in Galicia, Spain

In Galicia, Spain, liver copper concentrations, muscle zinc concentrations and kidney cadmium concentrations (in adult cattle) can exceed acceptable maximum concentrations which have been adopted by some countries. The aim was to calculate the contribution of cattle products to the daily intake of trace and toxic metals by humans in Galicia and to evaluate whether there was any health risk to consumers. This was done by comparing calculated intakes with published acceptable daily intake rates for toxic elements and with the accepted safe ranges for population mean intakes of the essential metals. Typically, the contribution of cattle meat and offal to the daily cadmium, lead and arsenic intake of people in Galicia was minimal because offal is rarely eaten. However, liver from older cattle, especially animals from relatively contaminated areas, could pose a health risk if offal was consumed in substantial quantities. Muscle and liver from Galician cattle that exceeded acceptable maximum concentrations for copper and zinc did not pose a risk to human health.
The Rho Guanine Nucleotide Exchange Factor Lsc Homo-oligomerizes and Is Negatively Regulated through Domains in Its Carboxyl Terminus That Are Absent in Novel Splenic Isoforms*

Rho GTPases control fundamental cellular processes, including cytoskeletal reorganization and transcription. Rho guanine nucleotide exchange factors (GEFs) compose a large (>65) and diverse family of related proteins that activate Rho GTPases. Lsc/p115-RhoGEF is a Rho-specific GEF required for normal B and T lymphocyte function. Despite its essential role in lymphocytes, Lsc/p115-RhoGEF signaling in vivo is not well understood. To define Lsc/p115-RhoGEF signaling pathways in vivo, we set out to identify proteins that interact with regulatory regions of Lsc. The 146-amino acid C terminus of Lsc contains a predicted coiled-coil domain, and we demonstrated that deletion of this C terminus confers a gain of function in vivo. Surprisingly, a yeast two-hybrid screen for proteins that interact with this regulatory C terminus isolated a larger C-terminal fragment of Lsc itself. Co-immunoprecipitation experiments in mammalian cells demonstrated that Lsc specifically homo-oligomerizes and that the coiled-coil domain in the C terminus is required for homo-oligomerization. Mutagenesis experiments revealed that homo-oligomerization and negative regulation are distinct functions of the C terminus. Two novel isoforms of Lsc found in the spleen lack portions of this C terminus, including the coiled-coil domain. Importantly, the C termini of both isoforms confer a gain of function and eliminate homo-oligomerization. These results define two important features of Lsc signaling. First, Lsc homo-oligomerizes and is negatively regulated through domains in its C terminus; and second, functionally distinct isoforms of Lsc lacking these domains are present in the spleen.
Weighted Additive Fuzzy Goal Programming Approach to Aggregate Production Planning

This study presents a new formulation of Weighted Additive fuzzy goal programming model developed by Yaghoobi and Tamiz (21). and Yaghoobi et al (22) for aggregate production planning (WAFGP- APP), The proposed formulation attempts to minimize total production and work force costs, carrying inventory costs and rates of changes in Work force. A real-world industrial case study demonstrates applicability of proposed model to practical APP decision problems. LINGO computer package has been used to solve final crisp linear programming problem package and getting optimal production plan.
Iridocyclitis in juvenile rheumatoid arthritis.

Eight of 70 children with juvenile rheumatoid arthritis have developed iridocyclitis. This complication occurred more frequently in patients with monoarticular and pauciarticular disease (29%) than in patients with polyarticular disease (2%). Seven of eight patients with iridocyclitis have monoarticular or pauciarticular disease; none has had prominent systemic manifestations or evidence of ankylosing spondylitis. Iridocyclitis preceded joint manifestations in two of the patients and followed arthritis by 1 to 10 years in six of the patients. Activity of iridocyclitis and arthritis seemed unrelated; four patients developed iridocyclitis while arthritis was inactive. In seven children iridocyclitis began insidiously without acute symptoms. Eye involvement has remained unilateral in six patients. Six children have had significant decrease in visual acuity, and six continue to have active ocular inflammation despite therapy. Iridocyclitis is potentially a major cause of disability in juvenile rheumatoid arthritis. Early signs and symptoms may be minimal. Patients at risk are those with limited forms of joint disease. Early detection and therapy are crucial for prevention of permanent ocular damage. Careful eye examination should be a routine part of physical examination of children with rheumatoid arthritis, and periodic slit lamp examinations should be performed even when arthritis is in remission.