Miracle-dz/UniFAR-FTUs huggingface dataset:
Clues to immune tolerance: the monogenic autoimmune syndromes

Autoimmune disease affects a significant proportion of the population. The etiology of most autoimmune diseases is largely unknown, but it is thought to be multifactorial with both environmental and genetic influences. Rare monogenic autoimmune diseases, however, offer an invaluable window into potential disease mechanisms. In this review, we will discuss the autoimmune polyglandular syndrome (APS1), the immunedysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome (IPEX), and autoimmune lymphoproliferative syndrome (ALPS). Significantly, the information gained from the study of these diseases has provided new insights into more common autoimmune disease and have yielded new diagnostics and therapeutic opportunities.
Methylene tetrahydrofolate reductase genotypes frequencies: association with toxicity and response to methotrexate in rheumatoid arthritis patients.

OBJECTIVES The purpose of this study was to determine the genotype/allele frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate (MTHFR) gene in Jordanian rheumatoid arthritis (RA) patients. In addition, the association between MTHFR gene C677T and A1298C polymorphisms and response to and toxicity of methotrexate (MTX) was evaluated. METHODS 159 adult rheumatoid arthritis ent Rheumatology Clinic at The Jordan University Hospital, between December, 2011 and April, 2012 were recruited into the study. Genomic DNA was extracted from leukocytes using Wizard Genomic DNA extraction Kit. The DNA extracts were amplified by polymerase chain reaction (PCR), and the PCR products were subjected to restriction enzymes to identify the C677T and A1298C genotypes. Genotype frequencies were identified and their relationship to some measures of MTX response and toxicity were evaluated. RESULTS The 677 TT genotype frequency was higher in RA patients (15.1%) compared to the healthy control group (5.9%) (odds ratio 3.09, 95% confidence interval (CI) 1.39-6.87, p-value=0.0056). No such differences were seen with the A1298C genotypes. The frequencies of 677T and 1298C variant alleles were 0.346 and 0.296, respectively. None of the change-in-disease-activity measurements in MTX-treated patients has a significant association with the various genotypes. There was no significant association between A1298C genotypes and "any MTX toxicity", but there was an association between C677T polymorphism and "any MTX toxicity" (p=0.037). In addition, there was no association between both SNPs and specific MTX adverse effects. However, some haplotypes or combinations of the C677T and A1298C genotypes were associated with certain MTX side effects. CONCLUSIONS More data from a larger number of RA patients are needed to evaluate the role of pharmacogenetic studies of MTHFR gene in predicting MTX response and toxicity.
Runtime Power Limiting of Parallel Applications on Intel Xeon Phi Processors

Energy-efficient computing is crucial to achieving exascale performance. Power capping and dynamic voltage/frequency scaling may be used to achieve energy savings. The Intel Xeon Phi implements a power capping strategy, where power thresholds are employed to dynamically set voltage/frequency at the runtime. By default, these power limits are much higher than the majority of applications would reach. Hence, this work aims to set the power limits according to the workload characteristics and application performance. Certain models, originally developed for the CPU performance and power, have been adapted here to determine power-limit thresholds in the Xeon Phi. Next, a procedure to select these thresholds dynamically is proposed, and its limitations outlined. When this runtime procedure along with static power-threshold assignment were compared with the default execution, energy savings ranging from 5% to 49% were observed, mostly for memory-intensive applications.
Gastrointestinal symptoms rating scale in coeliac disease patients on wheat starch-based gluten-free diets.

BACKGROUND A wheat starch-based gluten-free diet is widely adopted in the treatment of coeliac disease, even though the products contain trace amounts of gluten. The aim here was to establish whether such a diet sustains abdominal symptoms. METHODS The Gastrointestinal Symptom Rating Scale (GSRS) was applied to 58 coeliac disease patients on gluten-free diets and 110 non-coeliac controls. An estimate was made of daily dietary fibre and wheat starch-derived gluten. Psychological well-being was evaluated by a structured interview. Twenty-three coeliac patients consented to small-bowel biopsy. RESULTS The mean GSRS score in coeliac disease patients did not differ from that in control subjects. Poorer psychological well-being was associated with abdominal symptoms in coeliac patients, whereas the daily amount of wheat starch had no effect on GSRS score. Overall dietary compliance was good, and villous atrophy was found in only 2 out of 23 patients. The average fibre consumption, 13 g per day, was lower than recommended. CONCLUSIONS Wheat starch-based gluten-free products are well-tolerated in coeliac disease patients, provided that their diets are otherwise strict.
HER‐2/neu gene amplification in relation to expression of HER2 and HER3 proteins in patients with esophageal adenocarcinoma

Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors' knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance.
Profile of caregivers of Alzheimer’s disease patients attended at a reference center for cognitive disorders

This is a study on burden of caregivers of patients with Alzheimer’s disease attended at a Reference Center for Cognitive Disorders. Objective To evaluate the profile and burden on caregivers of patients with Alzheimer’s disease attended at a Reference Center for Cognitive Disorders. Methods We collected demographic information and data on the relationship with the patient from caregivers, and measured burden with the Zarit scale. The patients were evaluated with the following scales: the Cambridge Cognitive Test (CAMCOG); Mini Mental State Examination, the Neuropsychiatric Inventory for neuropsychiatry symptoms, and Functional Activities Questionnaire - FAQ for functional impairment. Results Of the 31 caregivers, 77.4% were female, predominantly, and daughters, having a mean age of 58.6 years, educational level of 8.1 years, 70% of caregivers co-resided with the patient and 71% did not work. The mean time as a caregiver was 3 years. Twenty-seven percent of the caregivers presented mild to severe burden. The variables presenting significant association with caregiver burden were scores on the NPI and CAMCOG. Conclusion The social demographic characteristics of the sample were similar to those of studies performed in other countries. The average time as a caregiver and the frequency of caregivers with mild to intense burden were lower than those reported in international studies. Neuropsychiatric symptoms and severity of cognitive decline were the main factors associated to burden in this sample of mostly mild to moderate demented AD patients. Further studies are necessary to verify whether the burden is indeed less intense in our milieu.
A Case Study of an Outsourcing Decision Project in a Large Public Organization

Phases in an outsourcing decision project are presented and critical issues are identified. First, there were different definitions of hosting and these different definitions made it unclear what the project was about and thereby the outcome of the project became unclear. This affected project commitment, project outcome project management, and project costs. Second, there were unclear descriptions of how the hosting was made in the organisation. The study suggests that had there been a clearer and more concise description of what the project was about and how the hosting was made a lot of the difficulties could have been avoided.
Use of an Electrostatic Dust Cloth for Self-Administered Home Allergen Collection

Abstract Most epidemiologic studies employ a vacuum cleaner used by a trained technician to collect household allergens. This approach is labor intensive, equipment dependent, and impractical if study subjects reside over a wide geographic area. We examined the feasibility of a self-administered dust collection method, using an electrostatic cloth sent by conventional mail, to obtain allergen measurements. Thirty-two nonasthmatic twins from the California Twin Program wiped areas in the family room, kitchen, and bedroom, according to standardized instructions, and returned the cloths by mail. Allergen concentrations for Der-p-1, Der-f-1, Fel-d-1, and Bla-g-2 were determined using ELISA, and intrahouse and room-to-room concentrations were compared. Der-p-1 and Fel-d-1 were found in most homes, with highest concentrations in bedrooms and kitchens, respectively. Der-f-1 and Bla-g-2 were rarely found. Intrahouse Der-p-1 and Fel-d-1 concentrations were highly correlated and statistically significant (for Der-p-1, bedroom vs. kitchen, p = .0003, bedroom vs. family room, p = .0001, and family room vs. kitchen, p = .002; for Fel-d-1, bedroom vs. kitchen, p = .0004, bedroom vs. family room, p < .0001, and family room vs. kitchen, p = .0001). Reported cat ownership was strongly correlated with household Fel-d-1 concentrations (p < .005). In another comparison from different homes of children enrolled in the La Casa atopy prevention study, allergen concentrations measured from dust collected by a single operator from the left and right half of the same room in 21 homes were compared. Levels of Bla-g-2, Der-p-1, and Fel-d-1 concentrations collected from right and left halves of the same room were highly correlated, with r2 ranging from . 7 to . 9, and were highly statistically significant (all p values < .01). We conclude that nonintrusive and self-administered dust collection, using commercially available electrostatic dust cloths, sent by conventional mail services, is a promising alternative to technician-collected vacuumed dust for measuring indoor allergens in population-based studies, although further validation of the method is necessary.
Feeding ecology of the Great Basin Rattlesnake (Crotalus lutosus, Viperidae)

Documenting variation in organismal traits is essential to understanding the ecology of natural populations. We relied on stomach contents of preserved specimens and literature records to assess ontogenetic, intersexual, temporal, and geographic variations in the feeding ecology of the North American Great Basin Rattlesnake (Crotalus lutosus Klauber, 1930). Snakes preyed mainly on rodents, occasionally on lizards, and less frequently on birds; squamate eggs and frogs were rarely eaten. There was a positive relationship between predator and prey size. The best predictors of this relationship were prey diameter as a function of snake body length and head size, underscoring the importance of prey diameter for gape-limited predators such as snakes. Crotalus lutosus displayed ontogenetic, sexual, and seasonal variations in diet. Smaller rattlesnakes fed predominantly on lizards, whereas larger individuals mostly fed on mammals. Females fed on liz- ards more often than males. The proportion of mammals in the diet was highest during the summer, a temporal variation that may be related to behavioral shifts in the diel activity and prey selectivity of C. lutosus, and (or) to differential abun- dance of rodents between seasons. Great Basin Rattlesnakes also displayed geographic variation in feeding habits, with snakes from the Great Basin Desert eating a higher proportion of lizards than serpents from the more northern Columbia Plateau. Resume ´ : Il est necessaire de connaoˆtre la variation des traits des organismes pour comprendre l'ecologie des populations naturelles. Nous avons examineles contenus d'estomacs de specimens de collection et consultela litterature pour quanti- fier les variations ontogenetiques, sexuelles, et saisonnieres dans le regime alimentaire du crotale du Grand Bassin (Cro- talus lutosus Klauber, 1930) en Amerique du Nord. Ce crotale se nourrit principalement de rongeurs, parfois de lezards, et moins frequemment d'oiseaux. Les œufs de squamates et les amphibiens sont tres rarement consommes. Il y a une relation positive entre la taille des proies et celle des serpents. La meilleure variable predictive de cette relation est le diametre de
Kauren‐19‐oic acid induces DNA damage followed by apoptosis in human leukemia cells

This study evaluated the potential cytotoxicity of the natural diterpenoids kauren‐19‐oic acid (KA), 14‐hydroxy‐kaurane (1) and xylopic acid (2), and semi‐synthetic derivatives of KA (3–5) towards human cancer cell lines (K562, HL60, MDA‐MB435 and SF295) and lymphocytes. Mouse erythrocytes were used to verify a possible hemolytic activity Cytotoxicity mechanisms were investigated in HL60 cells. KA showed a moderate antiproliferative effect in MTT assay towards all cancer cells (IC50, 9.1–14.3 µg ml−1). However, KA appeared not selective to cancer cells, since it also inhibited the lymphocytes proliferation (IC50, 12.6 µg ml−1). Unlike KA, compounds 1–5 displayed no cytotoxicity and were also free from antiproliferative and hemolytic effects, suggesting that the exocyclic double bond (C16) unit may be the active pharmacophore of KA cytotoxicity. KA‐treated HL60 cells displayed decreased proliferation (5‐bromo‐2';‐deoxyuridine incorporation assay) and topoisomerase I activity (DNA relaxation assay). These assays revealed that KA primarily intercalates with DNA and not with topoisomerase I. Fluorescence microscopy using AO/EB (acridine orange/ethidium bromide) staining indicated that KA can induce both apoptosis and necrosis in HL‐60 cell cultures, which corroborate the findings with MTT. From these findings, we conclude that KA, although demonstrating cytotoxic potential, may have a limited or poor therapeutic potential due to lack of selectivity to tumor cells. Further studies on the structure modification of KA and the mechanism of the new derivatives are currently in progress. Copyright © 2009 John Wiley & Sons, Ltd.
Comparison of methods for circulating cell-free DNA isolation using blood from cancer patients: impact on biomarker testing.

BACKGROUND The implementation of liquid biopsy for biomarker testing and response to treatment monitoring in cancer patients would presumable increase laboratory throughput, requiring the development of automated methods for circulating free DNA (cfDNA) isolation. METHODS The present study compares the MagNA Pure Compact (MPC) Nucleic Acid Isolation Kit I and Maxwell® RSC (MR) ccfDNA Plasma Kit and the later with QIAamp Circulating Nucleid Acid (QCNA) Kit using 57 plasma samples from cancer patients. cfDNA concentration was measured using the Qubit fluorometer. DNA fragments lengt were assessed using the Agilent 2100 Bioanalyzer. Circulating tumor DNA (ctDNA) was quantified by digital PCR (dPCR). RESULTS Firstly, we observed that MPC method significantly extracted less cfDNA than MR (P<0.0001). However, there were no significant differences in extraction yields of QCNA and MR kits. cfDNA isolation yield was also associated with tumor stage but not with tumor location. Secondly, an oligonucleosomal DNA ladder pattern was observed in 88% of the samples and significant differences in the recovery of mono-, di- and tri-nucleosomes DNA fragments were observed between MPC and MR methodologies. Finally, tumor mutation quantification on cfDNA was performed on 38 paired samples using digital PCR. Mutant allele fractions (MAFs) between paired samples were not significantly different. CONCLUSIONS Methods for isolation of cfDNA can affect DNA yield and molecular weight fractions recovery. These observations should be taken into account for cfDNA analysis in routine clinical practice.
Association of apolipoprotein E E4 with vascular dementia.

To the Editor. —It has recently been found that the frequency of the E4 allele of apolipoprotein E (apo E) is increased (about threefold) in familial and sporadic late-onset Alzheimer's disease (AD). 1 Apolipoprotein E is encoded by a single gene on chromosome 19; a common polymorphism is determined by alleles E2 , E3 , and E4 . The frequency of apo E E4 is around 0.10 to 0.16 in the general elderly population, and 0.36 to 0.48 in late-onset AD patients. This observation has given rise to a number of ethical and scientific questions regarding the necessity and meaning of apo E phenotyping in the general population. However, the specificity of risk is unknown. We assessed the frequency of apo E alleles in 87 AD and 21 vascular dementia patients and in 51 elderly hyperlipidemic nondemented controls. Diagnosis of probable AD (Mini-Mental State Examination score, 10.4 [SD,
Combined effect of water activity, pH and temperature on the growth of Clostridium botulinum from spore and vegetative cell inocula.

SUMMARY The initiation of vegetative growth by spores in Reinforced Clostridial Medium (RCM) adjusted to different water activities (aw) by the addition of NaCl or glycerol does not depend solely on the aw of the medium; minimum aw at which spores of Cl. botulinum types A, B and E could initiate growth were higher in the media containing NaCl. The minimum aw at which vegetative cell inocula could grow were similar to those at which spore inocula could initiate growth. The combined effect of lowering the pH and aw of the medium was to increase the minimum at which spores of types A and E could germinate and also increase the minimum at which spore and vegetative cell inocula of Cl. botulinum types A, B and E could initiate growth.
The prosody of maternal speech: infant age and context related changes

ABSTRACT The speech of 6 mothers to their healthy infants was examined longitudinally during the neonatal period and at 4, 12, and 24 months in a semi-naturalistic setting. Features of speech analysed were: contour of fundamental frequency, repetitiveness, timing (durations of vocalizations and pauses), tempo and MLU. The neonatal period was characterized by elongated pauses. During the 4-month period the extent of pitch contouring and repetitiveness was greater than at earlier or later ages. By 24 months, the duration of vocalizations and length of MLU became markedly greater. The period of intense face-to-face interaction around the fourth month proved to involve more changes in certain prosodic features. Some of the possible functions of these changes during this phase are discussed.
Helping older adults to help themselves: the role of mental health literacy in family members

ABSTRACT Objectives: Family members may play an important role in the health and well-being of older adults. However, little is known about the factors that influence the likelihood of family members supporting older relatives to seek help from mental health professionals for mental health concerns. Mental health literacy is associated with people's help-seeking intentions regarding their own mental health concerns, and some studies have suggested it may play a role in help-seeking on behalf of others. The purpose of this study was to investigate whether mental health literacy is associated with adults’ likelihood of supporting an older relative to seek professional help for mental health concerns. Method: Two hundred and sixty-three participants completed a measure of mental health literacy and responded to a hypothetical scenario by indicating their likelihood of supporting an older relative experiencing mental health problems to seek help from various sources. Results: Mental health literacy was positively associated with intentions to support older relative's help-seeking. Conclusions: Interventions to increase the mental health literacy of the relatives of older adults may lead to additional support for older adults’ help-seeking for mental health concerns.
Vitiligo and Autoimmune Thyroid Disorders

Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s).
The appearance and development of chemosensitivity in Rohon—Beard neurones of the Xenopus spinal cord

1. We have examined the onset and subsequent development of chemosensitivity in Rohon—Beard neurones from the Xenopus spinal cord. These cells become sensitive to bath‐applied γ‐aminobutyric acid (GABA) around stage 25 (early tailbud, about 1 d old), and remain so at least until stage 49 (9 d old). In contrast, a number of other neurotransmitter candidates tested caused no potential or conductance change during the same period.