Miracle-dz/UniFAR-FTUs huggingface dataset:
Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium “Care for CMMR-D” (C4CMMR-D)

Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as ‘constitutional mismatch repair-deficiency’ (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.
Network relationality in the tourism experience: staging sociality in homestays

ABSTRACT Drawing on the network sociality concept, this article investigates network relationality principles relating to shareable tourism experiences through peer-to-peer platforms. The methodology is based on a case study approach, using qualitative research tools. Four key principles of network relationality emerge from the findings: temporary belongingness, a priori empathy, technology as bridge to face-to-face interactions, and relational spaces. More than mere social interaction, network relationality focuses on the intensity of temporary relationships which shape the tourist experience beyond accommodation services.
New alkaloids from the seeds of Notopterygium incisum

Three new alkaloids, N-hexacosanoylanthranilic acid (1), N-octacosanoylanthranilic acid (2) and N-eicosanoyltyramine (3), along with 19 known compounds, were isolated from the seeds of Notopterygium incisum, whose rhizomes are used as a traditional Tibetan medicine. Their structures were elucidated by 1D, 2D NMR spectra and ESI-MS spectrometer evidence.
Chemokine Production by a Human Alveolar Epithelial Cell Line in Response to Mycobacterium tuberculosis

ABSTRACT To investigate the role of chemokines during the initial local response to Mycobacterium tuberculosis in the human lung, we studied chemokine production by the human alveolar epithelial cell line A549 after infection with M. tuberculosis. M. tuberculosis-infected A549 cells produced mRNAs and protein for monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) but not mRNAs for macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES. Chemokine production in response to M. tuberculosis was not dependent on production of tumor necrosis factor alpha, IL-1β, or IL-6. Two virulent clinical M. tuberculosis isolates, the virulent laboratory strain H37Rv, and the avirulent strain H37Ra elicited production of comparable concentrations of MCP-1 and IL-8, whereas killed M. tuberculosis and three Mycobacterium avium strains did not. The three virulent M. tuberculosis strains grew more rapidly than the avirulent M. tuberculosisstrain in the alveolar epithelial cell line, and the threeM. avium strains did not grow intracellularly. These findings suggest that intracellular growth is necessary for mycobacteria to elicit production of MCP-1 and IL-8 by alveolar epithelial cells but that virulence and the rate of intracellular growth do not correlate with chemokine production. Alveolar epithelial cells may contribute to the local inflammatory response in human tuberculosis by producing chemokines which attract monocytes, lymphocytes, and polymorphonuclear cells.
Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians.

OBJECTIVE To review data on the long-term effects of prenatal exposure to the diabetic intrauterine environment in the Pima Indians of Arizona. This population has high rates of Type 2 diabetes mellitus that has a strong genetic component and develops at young ages. METHODS Since 1965, Pima Indians at least 5 years old participated in a study of diabetes and its complications. This study consisted of biennial examinations with measurements of obesity and glucose tolerance and of glucose tolerance testing during pregnancy. The longitudinal nature of the study has permitted comparisons of data collected on children and young adults whose mothers were tested during pregnancy. RESULTS Offspring of women who had diabetes during pregnancy were more obese and had a higher prevalence of Type 2 diabetes. Exposure to the diabetic intrauterine environment was responsible for about 40% of Type 2 diabetes in 5-19-year-old children between 1987 and 1996--approximately twice the attributable risk found between 1967 and 1976. Over 70% of persons with prenatal exposure have Type 2 diabetes at 25-34 years of age. CONCLUSIONS The effects of the diabetic pregnancy can be thought of as a vicious cycle, with consequences for the offspring extending well beyond the neonatal period. The young woman whose mother had diabetes during pregnancy is at risk of perpetuating the cycle by developing diabetes by her childbearing years. In this population, much of the increase in childhood Type 2 diabetes can be attributed to the diabetic intrauterine environment, which may be a factor in the alarming rise of this disease nationally.
Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription

Alzheimer's disease (AD) is the most commonly diagnosed form of dementia in the elderly. Predominantly this disease is sporadic in nature with only a small percentage of patients exhibiting a familial trait. Early‐onset AD may be explained by single gene defects; however, most AD cases are late onset (> 65 years) and, although there is no known definite cause for this form of the disease, there are several known risk factors. Of these, the ε4 allele of the apolipoprotein E (apoE) gene (APOE) is a major risk factor. The ε4 allele of APOE is one of three (ɛ2 ɛ3 and ɛ4) common alleles generated by cysteine/arginine substitutions at two polymorphic sites. The possession of the ɛ4 allele is recognized as the most common identifiable genetic risk factor for late‐onset AD across most populations. Unlike the pathogenic mutations in the amyloid precursor or those in the presenilins, APOEɛ4 alleles increase the risk for AD but do not guarantee disease, even when present in homozygosity. In addition to the cysteine/arginine polymorphisms at the ɛ2/ɛ3/ɛ4 locus, polymorphisms within the proximal promoter of the APOE gene may lead to increased apoE levels by altering transcription of the APOE gene. Here we review the genetic and biochemical evidence supporting the hypothesis that regulation of apoE protein levels may contribute to the risk of AD, distinct from the well known polymorphisms at the ɛ2/ɛ3/ɛ4 locus.
Orthotic devices for the treatment of tennis elbow.

BACKGROUND Lateral epicondylitis (tennis elbow) is a frequently reported condition. A wide variety of treatment strategies has been described. As of yet, no optimal strategy has been identified. OBJECTIVES To assess the effectiveness of orthotic devices for the treatment of tennis elbow. SEARCH STRATEGY We searched Medline, Embase, CINAHL, the Cochrane Controlled Trial Register, Current Contents up to May 1999 and reference lists from all retrieved articles. Experts on the subjects were approached for additional trials. SELECTION CRITERIA All randomised clinical trials (RCT) describing individuals with diagnosed lateral epicondylitis and comparing the use of an orthotic device as a treatment strategy were evaluated for inclusion. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed the validity of the included trials and extracted data on relevant outcome measures. Dichotomous outcomes were expressed as Relative Risks (RRs) and continuous outcomes as Standardised Mean Differences (SMD), both with corresponding 95% confidence intervals (95% CI). Statistical pooling and subgroup analyses were intended MAIN RESULTS Five RCTs (N per group 7-49) were included. Validity score ranged from 3-9 positive items out of 11. Subgroup analyses were not performed due to the small number of trials. The limited number of included trials present few outcome measures and limited long-term results. Pooling was not possible due to large heterogeneity amongst trials. REVIEWER'S CONCLUSIONS No definitive conclusions can be drawn concerning effectiveness of orthotic devices for lateral epicondylitis. More well-designed and well-conducted RCTs of sufficient power are warranted.
Reciprocal relationship between methylation status and loss of heterozygosity at the p14ARF locus in Australian and South African hepatocellular carcinomas

Abstract Chromosome 9p21, a locus comprising the tumor suppressor genes (TSG) p16INK4a and p14ARF, is a common region of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC). p14ARF shares exon 2 with p16 in a different reading frame. p14 binds to MDM2 resulting in a stabilization of functional p53. This study examined the roles of p14, p16 and p53 in hepatocarcinogenesis, in 37 Australian and 24 South African patients. LOH at 9p21 and 17p13.1, p14 and p16 mutation analysis, p14 and p16 promoter methylation and p14, p16 and p53 protein expression was examined. LOH at 9p21 was detected more frequently in South African HCC (P = 0.04). Comparable rates of p53 LOH were observed in Australian and South African HCC (10/22, 45%vs 13/22, 59%, respectively). Hypermethylation of the p14 promoter was more prevalent in Australian HCC than in South African HCC (17/37, 46%vs 7/24, 29%, respectively). In Australian HCC the prevalence of p14 methylation increased with age (P = 0.03). p16 promoter methylation was observed in 12/37 (32%) and 6/24 (25%) in Australian and South African HCC, respectively. Loss of p16 protein expression was detected in 14/36 Australian HCC whereas p53 protein expression was detected in 9/36. Significantly, a reciprocal relationship between 9p21 LOH and p14 promoter hypermethylation was observed (P≤0.05). No significant association between p14 and p53 was seen in this study. The reciprocal relationship identified indicates different pathways of tumorigenesis and likely reflects different etiologies of HCC in the two countries.
Maternal Enteroviral Infection During Pregnancy as a Risk Factor for ChildHood IDDM: A Population-Based Case-Control Study

Using the nationwide childhood-onset diabetes register in Sweden, we were able to trace children who contracted diabetes before the age of 15 years and who were born at a specific hospital in Sweden where maternal sera from delivery had been stored during the years 1969-1989. Sera obtained at delivery from 57 mothers of diabetic children were compared with sera from 203 mothers of control subjects who were delivered at the same hospital during the same time period. The sera were analyzed blindly using a group-specific enzyme-linked immunosorbent assay for enteroviral IgG and IgM antibodies before and after urea wash as an avidity test. On the same plates, IgG antibodies to herpes, mumps, and toxoplasmosis were analyzed. The mean absorbance values of enteroviral IgG antibodies against enteroviral antigens (echo30, coxsackie B5, and echo9) were significantly higher among mothers whose children later developed diabetes (P = 0.002, P = 0.02, and P = 0.04, respectively). When reduction in activity after urea wash, indicating recently formed antibodies, was compared, the differences were even more pronounced (P < 0.001 for all three antigens). No significant differences were found for antibodies against herpes (all types), herpes type 2, mumps, or toxoplasmosis. When IgM activity and/or a significant decrease in avidity index, an indication of recent enterovirus infection, was used as a risk exposure, the odds ratio standardized for year of birth (95% confidence interval) was 3.19 (1.39–7.30). We conclude that the results of this study indicate that enteroviral infection during pregnancy is a risk factor for childhood-onset diabetes in the offspring. Whether one or several viruses in the enterovirus group are responsible remains to be discovered.
E-learning systems in higher education institutions: An outlook of their use in the Western Balkan Region

This study provides a review of the literature on e-learning systems evolution and environments. The argument is that e-learning systems should be embedded in the core strategy of the institution. To support this premise, studies for e-learning are analyzed and six recommendations are drawn for universities to follow in order to have successful e-learning environments. The main contribution of this study, however, is the identification of the trends and statistics regarding the e-learning usage in the Balkan region. These stats are identified through a survey conducted in 40 universities in 10 countries from this region. The results show that more than 70% of the universities have adopted LMS, which does not fall short behind when compared with universities in the world. Also, the results show that around 64% of the private universities develop LMS in-house, compared with around 38% of the public universities, which have funding from the governments and can purchase vendor based solutions. However, the results from the survey suggest that public universities in these countries are more prone to open-source rather than vendor based.
Risk of Stress Urinary Incontinence Twelve Years After the First Pregnancy and Delivery

OBJECTIVE: To estimate the impact of onset of stress urinary incontinence in first pregnancy or postpartum period, for the risk of symptoms 12 years after the first delivery. METHODS: In a longitudinal cohort study, 241 women answered validated questions about stress urinary incontinence after first delivery and 12 years later. RESULTS: Twelve years after first delivery the prevalence of stress urinary incontinence was 42% (102 of 241). The 12-year incidence was 30% (44 of 146). The prevalence of stress urinary incontinence 12 years after first pregnancy and delivery was significantly higher (P<.01) in women with onset during first pregnancy (56%, 37 of 66) and in women with onset shortly after delivery (78%, 14 of 18) compared with those without initial symptoms (30%, 44 of 146). In 70 women who had onset of symptoms during first pregnancy or shortly after the delivery but remission 3 months postpartum, a total of 40 (57%) had stress urinary incontinence 12 years later. In 11 women with onset of symptoms during the first pregnancy or shortly after delivery but no remission 3 months postpartum, a total of 10 (91%) had stress urinary incontinence 12 years later. Cesarean during first delivery was significantly associated with a lower risk of incontinence. Other obstetric factors were not significantly associated with the risk of incontinence 12 years later. Patients who were overweight before their first pregnancy were at increased risk. CONCLUSION: Onset of stress urinary incontinence during first pregnancy or puerperal period carries an increased risk of long-lasting symptoms. LEVEL OF EVIDENCE: II-2
Natural bioactive substances in milk and colostrum: effects on the arterial blood pressure system

High blood pressure is a significant public health problem worldwide which is associated with increased risk of cardiovascular disease, stroke, and renal disease. The development of this disease is influenced by genetic and environmental factors. The results of many studies have linked increased consumption of milk and milk products with lower blood pressure and reduced risk of hypertension. The intake of several minerals found in milk has been demonstrated to have an inverse relationship with blood pressure. Peptides formed during the digestion of milk proteins have also been demonstrated to have a blood pressure lowering effect. Other components in milk that have been examined for their effects on blood pressure have been less promising. More recent data indicate that a dietary pattern that is low in fat, with fruits, vegetables, and low fat dairy products can significantly reduce blood pressure and lower risk of developing high blood pressure.
Iodide in CTAB prevents gold nanorod formation.

The gold nanocrystal seed-mediated approach using cetyltrimethylammonium bromide (CTAB) as a stabilizing surfactant is commonly used to make large quantities of monodisperse gold nanorods. This method, however, has been at times difficult to reproduce in different laboratories. We recently showed [Smith, D. K. ; Korgel, B. A. Langmuir 2008, 24, 644-649] that a very low concentration impurity in CTAB obtained from some suppliers prevents nanorod growth but were not able to identify the impurity. Here, we report that the impurity is iodide. Inductively coupled plasma mass spectroscopy (ICP-MS) revealed that iodide concentrations vary in CTAB from different suppliers, from less than 2.75 ppm up to 840 ppm. When CTAB with iodide concentrations greater than 50 ppm is used, nanorods do not form and the product consists entirely of spherical nanocrystals. Iodide slows the reduction of Au(III) to Au0. Iodide adsorption on Au {111} surfaces inhibits nanorod growth.
Chemical, biological, and immunochemical properties of the Chlamydia psittaci lipopolysaccharide

The lipopolysaccharide (LPS) of Chlamydia psittaci was extracted from yolk sac-grown elementary bodies, purified, and characterized chemically, immunochemically, and biologically. The LPS contained D-galactosamine, D-glucosamine, phosphorus, long-chain fatty acids, and 3-deoxy-D-manno-2-octulosonic acid in the molar ratio of approximately 1:2:2:6:5. The antigenic properties of the isolated LPS were compared with those of the LPS from Chlamydia trachomatis and Salmonella minnesota Re by the passive hemolysis and passive hemolysis inhibition tests, absorption, hydrolysis kinetics, and Western blot analysis with rabbit polyclonal antisera against chlamydiae and with a mouse monoclonal antibody recognizing a genus-specific epitope of chlamydial LPS. Two antigenic determinants were identified, one of which was chlamydia specific and the other of which was cross-reactive with Re LPS. Both determinants were destroyed during acid hydrolysis, whereby a third antigen specificity was exposed which was indistinguishable from the lipid A antigenicity. In rabbit polyclonal antisera prepared against Formalin-killed elementary bodies or detergent-solubilized membranes, two antibody specificities were differentiated. One of these was chlamydia specific, and the other was cross-reactive with Re LPS. The LPS of C. psittaci was inactive within typical endotoxin parameters (lethal toxicity, pyrogenicity, local Shwartzman reactivity); it was, however, active in some in vitro assays, such as those testing for mouse B-cell mitogenicity and the induction of prostaglandin E2 in mouse peritoneal macrophages.
In vivo EVALUATION OF PHOTOPROTECTION AGAINST CHRONIC ULTRAVIOLET‐A IRRADIATION BY A NEW SUNSCREEN MEXORYL® SX *

Abstract— In a previous study on the hairless mouse it was shown that sub‐erythemal doses of pure UV‐A enhanced the numerous changes normally observed during chronological aging. A new sunscreen (a bis‐benzylidene campho sulfonic acid derivative) has been synthesized in our research laboratory (Λmax: 345 nm, ε: 47000). Its photoprotective properties against UV‐A induced damages were assessed in our mouse model. Three month old albino hairless mice were exposed for 1 y to suberythemal doses (35 J/cm2) of UV‐A obtained from a xenon source filtered through a WG 345 filter. One group of animals was exposed untreated, the other received a formulation containing 5% of the sunscreen prior to irradiation. At the end of the study the cutaneous properties of protected mice were compared to those of unprotected animals and to 3 and 15 month old unirradiated controls. We found that the visible changes induced by UV‐A irradiation were mainly sagging and wrinkling. Histological and electron microscopic alterations consisted of hyperkeratosis, increased density of elastic fibers with alteration of fiber orientation and increased glycosaminoglycan deposits. Biochemical changes consisted of decreases in total collagen and collagen hydroxylation and increases in both collagen III/I + III ratio and fibronectin biosynthesis. All these changes were reduced or abolished by the sunscreen.
Medication safety in residential aged-care facilities: a perspective

Medication safety must be tailored to the distinctive issues in residential aged-care facilities (RACFs). The health and functional characteristics of their residents are different to those of hospital inpatients and community-dwelling older adults, and there are unique staffing and management issues. Understanding the aetiology and epidemiology of drug-related problems is vital in developing methods to improve patient safety. In this perspective review, we discuss tools that are used to quantify exposure to ‘high-risk’ medications and their evaluation in residential aged-care settings. Drug withdrawal interventions are described as a potential way to reduce adverse drug events in RACFs. Multidisciplinary professional interventions, education programs and improved communication between health professionals have been shown to improve medication safety in RACFs. Technological advances and other administrative strategies may also improve resident safety. This perspective addresses issues in medication safety facing RACFs and methods to improve the safety of medicines for their residents.
The Social Inclusion and Inequality Nexus:EUversus non‐EUmigrants

This study examines the relationship between social inclusions of migrant and income inequality. Both positive and negative impacts of social inclusion on income inequality have been observed in the previous literature. This study specifically considers two types of migration flow: migration flow from EU and migration flow from non‐EU. The aim of this article is twofold: 1) is there a strong association between social inclusion of migrants and income inequality, 2) is there any different impact of social inclusion of two types of migrants (EU vs non‐EU)? Using data from 33 mainly European countries over the period 2003‐2015 and controlling for savings rate, arable land rate and age‐dependency ratio, our results indicate that there is a significant negative relationship between social inclusion and income inequality. In particular, we find that social inclusion from non‐EU migrants significantly reduces income inequality compare with EU migrants.