Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of basophil activation by flow cytometry in pediatric house dust mite allergy

Detection of allergen‐induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. The aim of this study was to assess the potential of this technique for the diagnosis of pediatric house dust mite allergy. Quantification of total and specific IgE and basophil activation test were performed to evaluate mite allergic (n = 24), atopic (n = 23), and non‐allergic children (n = 9). Allergen‐induced basophil activation was detected as a CD63‐upregulation. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut‐off value of activated basophils discriminating mite allergic and non‐allergic children. ROC curve analysis yielded a threshold value of 18% activated basophils when mite‐sensitized and atopic children were studied [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.97–1.01, p < 0.001] with a sensitivity and specificity of 96% for 16 μg/ml mite extract. Analysis of the data obtained with 1.6 μg/ml mite extract defined a cut‐off value of 8% activated basophils (AUC = 0.96, 95% CI = 0.91–1.01; p < 0.001) with a sensitivity of 82% and specificity of 100%. Comparison between mite allergic and non‐allergic children produced a cut‐off of 8% activated basophils (AUC = 1.0) with 16 μg/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 μg/ml extract (AUC = 97%, 95% CI = 0.92–1.02; p < 0.001) but sensitivity decreased to 83%. Two atopic children showed negative skin prick and basophil activation tests and high specific IgE (>43 kU/l) values for Dermatophagoides pteronyssinus allergen. They also showed positive prick (wheal diameter >1.0 cm) and basophil activation (>87%) tests and high specific IgE (>100 kU/l) with shrimp allergen. Shrimp sensitization was demonstrated by high levels of Pen a 1‐specific IgE (>100 kU/l). Cross‐reactivity between mite and shrimp was confirmed by fluorescence enzyme immunoassay (FEIA‐CAP) inhibition study in these two cases. This study demonstrated that the analysis of allergen‐induced CD63 upregulation by flow cytometry is a reliable tool for diagnosis of mite allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity. Furthermore, this method can provide additional information in case of disagreement between in vivo and in vitro test results.
Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non‐atopic children. We hypothesized that locally produced total IgE and allergen‐specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)‐specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non‐atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP‐specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL‐2 receptors (sIL‐2R), soluble CD23 (sCD23), and IL‐6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non‐atopic individuals. Median values of DP‐specific IgE and IgA antibodies were significantly higher in atopics than in non‐atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP‐specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non‐atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL‐2R, and IL‐6 levels. The levels of DP‐specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL‐2R, sCD23, and IL‐6. The presence of total IgE and DP‐specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally‐produced total IgE and DP‐specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.
A new PTGDR promoter polymorphism in a population of children with asthma

Recently, functional genetic variants of the PTGDR gene have been associated with asthma. The objective of this work was to study polymorphisms of the promoter region of PTGDR and their haplotype and diplotype combinations in a Spanish population of children with asthma. In this study, 200 Caucasian individuals were included. Asthma was specialist–physician diagnosed according to the ATS criteria. The polymorphisms were analyzed by direct sequencing. In the study, the new polymorphism (‐613C > T) in the promoter region of PTGDR was analyzed. The CT genotype was more common in controls (17%) than in patients with asthma (1%) (p‐value = 0.0003; OR, 0.057; 95% CI, 0.007–0.441). The CCCT CCCC diplotype (promoter positions ‐613, ‐549, ‐441, and ‐197) was more frequent in the group of patients with asthma [Fisher’s p‐value = 0.012; OR, 10.24; 95% CI (1.25–83.68)]; this diplotype is unambiguous. To our knowledge, this is the first study of ‐613C > T PTGDR polymorphism in patients. This analysis provides more complete information on influence of diplotype combinations of PTGDR polymorphisms in asthma.
Fish allergy in childhood

Fish and its derived products play an important role in human nutrition, but they may also be a potent food allergen. Fish can be an ingested, contact, and inhalant allergen. Gad c I, a Parvalbumin, the major allergen in codfish, is considered as fish and amphibian pan‐allergen. Prevalence of fish allergy appears to depend on the amount of fish eaten in the local diet. In Europe, the highest consumption occurs in Scandinavian countries, Spain and Portugal. In Spain, fish is the third most frequent allergen in children under 2 yr of age after egg and cow’s milk. An adverse reaction to fish may be of non‐allergic origin, due to food contamination or newly formed toxic products, but the most frequent type of adverse reactions to fish are immunologic‐mediated reactions (allergic reactions). Such allergic reactions may be both IgE‐mediated and non‐IgE‐mediated. Most cases are IgE‐mediated, due to ingestion or contact with fish or as a result of inhalation of cooking vapors. Some children develop non‐IgE‐mediated type allergies such as food protein induced enterocolitis syndrome. The clinical symptoms related to IgE‐mediated fish allergy are most frequently acute urticaria and angioedema as well as mild oral symptoms, worsening of atopic dermatitis, respiratory symptoms such as rhinitis or asthma, and gastrointestinal symptoms such as nausea and vomiting. Anaphylaxis may also occur. Among all the species studied, those from the Tunidae and Xiphiidae families appear to be the least allergenic.
Predictors of Non-use of Condoms Among Drug Users in China: implications for HIV harm reduction

In China, the majority of drug users do not use condoms when they engage in premarital and extramarital sex behaviors. The first step to promote safer sex is to identify factors associated with the non-use of condoms. Using a sample of 450 heroin users from a detoxification center in China, this short report documents and examines predictors of non-use of condoms. The results show that non-use of a condom is associated with unmarried males of low income. In addition, attitude factors are important; those who have heard of 'safer sex' and believe in the importance of condom use are more likely to use a condom in premarital and extramarital sex. The findings suggest the importance of educational campaigns to promote the awareness of condom use and its utility.
Clinical effects of a Long‐term Educational Program for Children with Asthma – Aironet®. A 1‐yr randomized controlled trial

Educational self‐management programs for children with asthma have now become a routine feature in the management of the disease, as international guidelines underline. We designed this trial to find out whether Aironet®, an educational program developed for children with asthma, influenced asthma severity and improved parents’ knowledge of the disease. In a multicenter, prospective, randomized controlled trial we enrolled 123 children, 72 boys, mean age 8.78 yr (±2.33 s.d.), with intermittent or mild persistent asthma. Participants were randomly assigned to an education group, who received Aironet® at baseline and 2 months later (60 children), or to a control group who did not (63 children). Follow‐up lasted 12 months and included out‐patient clinic visits and spirometry at 2, 4 and 12 months. At baseline and at 12 months follow‐up, parents were questioned about their knowledge of asthma, and their children’s asthmatic attacks, use of systemic corticosteroids, family physician or hospital emergency room visits, hospitalizations and asthma‐related school absences. Questionnaire replies at 12‐month follow‐up reported significantly fewer asthma attacks in patients who received the program than in those who did not (1.65 ± 1.21 vs. 2.34 ± 1.73; p < 0.05). For the subgroup of children who had ≥3 asthma attacks at baseline, parents’ knowledge improved significantly more in the educational group than in the control group. The out‐patient educational program Aironet® reduces the number of asthma attacks in children with intermittent or mild persistent asthma and improves knowledge of the disease.
Maternal urinary β‐core fragment of hCG/creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy

Our aim was to evaluate the potential value of the ratio of the maternal urinary beta‐core fragment of human chorionic gonadotropin (βC‐hCG) to creatinine (Cr) in discriminating between normal pregnancies and pregnancies associated with fetal chromosomal abnormalities. We hypothesized that pregnancies with fetal chromosomal abnormalities had abnormal quantities of βC‐hCG in the urine. The aims of the present study were to investigate retrospectively whether maternal urinary ratios of βC‐hCG/Cr are abnormal in women carrying fetuses with chromosome aberrations and to determine normative median values and a reference range for βC‐hCG/Cr between 14 and 19 weeks' gestation. Maternal urinary βC‐hCG and Cr concentrations were measured in 150 healthy women from 14 to 19 weeks and compared with ten cases of fetal chromosomal abnormalities matched for gestational age. The preliminary cut‐off points corresponded to 0·29 multiple of the normal median (MOM) and 2·83 MOM, which were equivalent to the tenth and 90th centiles of the normal range. Of ten cases of fetal chromosomal abnormalities, one out of one (100 per cent) case with trisomy 18 and three of four (75 per cent) cases of variant 9 chromosome had low βC‐hCG/Cr (≤0·29 MOM). One of five (20 per cent) cases with Down syndrome had elevated βC‐hCG/Cr (≤2·83 MOM). Urinary βC‐hCG/Cr ratios obtained in the second trimester may be useful for improved detection efficiency of Down syndrome, trisomy 18, and inversion of chromosome 9. Second‐trimester maternal urinary βC‐hCG/Cr should be investigated further as a potential marker for fetal chromosome anomalies.
Food allergy after liver transplantation in children: a prospective study

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non‐food allergy group (10.2 months vs. 68.9 months, p < 0.05). Food allergy has been developed within 1 yr in 5, and in 20 months in one patient after OLT. All six patients had cow’s milk and egg allergy after OLT. Five children developed wheat, one children developed lentil and another one developed peach allergy in addition to cow’s milk and egg allergy. Out of six food‐allergic patients after OLT, four children developed Epstein–Barr virus (EBV) infection prior to food allergy. Before OLT, TECs and total IgE levels were not differed among food allergic and non‐food allergic patients (p > 0.05). Mean of TECs were significantly higher in food allergic group compared to non‐food allergic group at each time point after OLT (p < 0.05). Though statistically insignificant, mean of total IgE levels were also higher in the food allergic group (p > 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.
The diagnosis of IgE‐mediated food allergy in childhood

IgE‐mediated food allergy is a common condition in childhood and a recognized public health concern. An accurate diagnosis of food allergy facilitates the avoidance of the allergen – and cross‐reactive allergens – and allows for safe dietary expansion. The diagnosis of food allergy relies on a combination of rigorous history, physical examination, allergy tests [skin prick tests (SPT) and/or serum‐specific IgE] and oral food challenges. Diagnostic cut‐off values for SPT and specific IgE results have improved the diagnosis of food allergy and thereby reduced the need to perform oral food challenges. This clinical case series seeks to highlight a contemporary approach to the diagnosis of food allergy in children strategies.
Lifelong learning, its facilitators and barriers in primary care settings: a qualitative study

Although the need for lifelong learning, with implications for the development of all primary healthcare team members has been emphasized by policy documents and the new General Medical Services (nGMS) contracts, inter-professional facilitators and barriers for lifelong learning have not been fully investigated. This article presents common facilitators and barriers to lifelong learning as perceived by both implementers and recipients of a regional primary care workforce development strategy. It is based on a wider formative explorative evaluation study involving semi-structured interviews and focus groups in 22 primary care trusts (PCTs) and associated general practitioner (GP) practices in South East England. Twenty-nine strategy implementers, comprising Associate Deans, Lifelong Learning Advisors, Primary Care Workforce Tutors, GP Tutors, PCT Educators, were interviewed and 12 took part in two focus groups. Thirty-one strategy recipients, GPs, Practice Managers, Practice Nurses were also interviewed. Interviews and focus groups were recorded, transcribed verbatim and analysed using thematic framework analysis. This study provides evidence that traditional cultures, marked by a lack of inter-professional learning still exist in primary care settings and may obscure lifelong learning. Common facilitators to both implementers and recipients were influential professional networks, managerial and peer support, recent policy changes and protected learning time. Common barriers to both groups were insufficient organizational support, time constraints, lack of funding and boundaries between PCTs and general practices. Strategies to overcome barriers and reinforce facilitators need further exploration. PCTs and general practices should become learning organizations that provide continuous learning opportunities, support collaboration and foster links between organizations and individuals. Lifelong learning development can only flourish when a support system is created, composed of clearly allocated time, budgets and a sustainable support framework.
The clinical expression of asthma in schoolchildren has changed between 1996 and 2006

Andersson M, Bjerg A, Forsberg B, Lundbäck B, Rönmark E. The clinical expression of asthma in schoolchildren has changed between 1996 and 2006. Pediatr Allergy Immunol 2010: 21: 859–866. © 2010 John Wiley & Sons A/S
Synthesis and Antineoplastic Activity of O‐Alkylated Derivatives of 7‐Hydroximinoandrost‐5‐ene Steroids

Varied positioning of the hydroximino group on the parental steroid skeleton results in remarkable changes in the antineoplastic activity profile of the compounds. Here, the compound 7‐oximino‐5‐androstene and its O‐alkylated derivatives have been prepared and screened for cytotoxic and aromatase inhibitory activity. The steroidal 7‐oximino ether derivatives exhibited insignificant cytotoxic effects when screened against three cancer cell lines, MCF‐7 (breast), NCl‐H460 (lung), and SF‐268 (CNS) at 100 μM. However, the imidazolyl‐substituted steroidal oxime ethers displayed moderate inhibition of cytochrome P450 aromatase.
Cell Cycle Arrest and Apoptosis Induction by an Anticancer Chalcone Epoxide

Safe and effective chemotherapeutic agents for the treatment of pancreatic cancer remain elusive. We found that chalcone epoxides (1,3‐diaryl‐2,3‐epoxypropanones) inhibited growth in two pancreatic cancer cell lines, BxPC‐3 and MIA PaCa‐2. Three compounds were active, with GI50 values of 5.6 to 15.8 µM. Compound 4a, 1,3‐bis‐(3,4,5‐trimethoxyphenyl)‐2,3‐epoxypropanone, had an average GI50 of 14.1 µM in the NCI 60‐cell‐line panel. To investigate the mode of action, cell cycle analyses of BxPC‐3 cells were carried out. Treatment of cells with 50 µM 4a resulted in dramatic accumulation at G2/M (61% after 12 h for 4a vs. 15% for untreated cells). The cells rapidly entered apoptosis. After 12 h, 26% of cells treated with 50 µM 4a had entered apoptosis vs. 4% for cells treated with 100 µM etoposide and 2% for untreated cells. Compound 4a interfered with paclitaxel enhancement of tubulin polymerization, suggesting microtubules as the site of action. Reaction of thiol nucleophiles with 4a under basic conditions resulted in epoxide ring‐opening and retroaldol fragmentation, yielding alkylated thiol. MALDI mass spectrometry showed that retroaldol reaction occurred upon treatment of β‐tubulin with 4a. The site of alkylation was identified as Cys354. Chalcone epoxides warrant further study as potential agents for treatment of cancer.
Diagnosis and Management of Pituitary Carcinomas

Pituitary carcinomas are rare, making up some 0.2% of all pituitary tumors, but represent a particular challenge to clinical practice. The diagnosis of a pituitary carcinoma requires evidence of metastatic disease, either outside the central nervous system (CNS) or as separate noncontiguous foci within the CNS. They may present as typical pituitary adenomas, which reveal their malignant character only as time progresses, or as peculiarly aggressive tumors ab initio. Recent changes in histopathological classification have clarified many of the features of such tumors, including immunohistochemical staining for Ki-67 and p53, but to date none has been found to be pathognomonic. The majority of carcinomas are secretory, usually arising from corticotroph tumors or prolactinomas, but all histological types and secretory patterns are represented. Treatment is by surgery, transsphenoidal wherever possible, and conventional and stereotactic radiotherapy, but ultimately, a plethora of therapies may be required, including various attempts at medical therapy. Chemotherapy in some instances probably prolongs survival, but, in general, their progress from the diagnosis of carcinomatous changes is progressive and inexorable. However, we do not believe there will be any real prospect of long-term survival until the development and use of therapies targeted at specific molecular abnormalities.
Abstract P5-18-01: Pertuzumab (P) in combination with trastuzumab (T) and docetaxel (D) in elderly patients with HER2-positive metastatic breast cancer in the CLEOPATRA study

Background: The incidence of cancer increases with age as does the risk of treatment-related adverse events (AEs) due to underlying comorbidities. A better understanding of cancer therapy-related AEs in elderly pts may help identify the optimal therapy by balancing treatment benefit and risk. CLEOPATRA, a double-blind Phase III trial, compared placebo (Pla)+T+D with P+T+D in pts with HER2-positive 1L MBC (Baselga 2012). Here we report safety and efficacy by age group. Methods: P/Pla: 840 mg initial dose, 420 mg q3w iv; T: 8 mg/kg initial dose, 6 mg/kg q3w iv; D: 75 mg/m 2 q3w iv, escalating to 100 mg/m 2 if tolerated. P/Pla+T were given until progressive disease (PD) or unacceptable toxicity. At least 6 cycles of D were recommended; 6 cycles were allowed at investigators9 discretion. At baseline, pts were required to have ECOG PS of 0 or 1, LVEF ≥50% and no decline to 2 or its equivalent. The primary endpoint was independently assessed PFS; secondary endpoints included overall survival, objective response, safety. Results: In the safety population, 678 pts (332 Pla arm, 346 P arm) were 2 /week) and 8 (1–35) in the P arm (24.5 mg/m 2 /week). The median number of D cycles was lower in pts ≥65 yrs, with 6.5 (1–26) in the Pla arm (24.8 mg/m 2 /week) and 6 (1–16) in the P arm (24.8 mg/m 2 /week). In elderly pts, the incidence of diarrhea, fatigue, and dysgeusia appeared to be higher in both arms, whereas neutropenia and febrile neutropenia were reported less frequently. Grade ≥3 diarrhea was reported in 4.8% (Pla arm) and 6.6% (P arm) of pts Conclusions: Overall, the AE profile reported in CLEOPATRA suggests that, in pts with good performance status, the use of P should not be limited by age. Therapy with P+T+D resulted in improved efficacy in pts aged Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-01.
A less conservative stability test for second-order linear time-varying vector differential equations

System stability and stability bounds play an essential role in control theory. This note is concerned with the exponential stability of a class of second-order linear time-varying vector differential equations with real piecewise continuous coefficient matrices. A less conservative explicit condition for stability of such a system is derived using the matrix measure theory and a more accurate upper bound for the decay exponent of its stable solution is established. Examples are included for illustration.