Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical characteristics and mutation analysis of two Chinese children with 17a-hydroxylase/17,20-lyase deficiency.

Combined with the literature, recognize the clinical features and molecular genetic mechanism of the disease. 17a-hydroxylase/17,20-lyase deficiency, a rare form of congenital adrenal hyperplasia, is caused by mutations in the cytochrome P450c17 gene (CYP17A1), and characterized by hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism. We presented the clinical and biochemical characterization in two patients (a 13 year-old girl (46, XX) with hypokalemia and lack of pubertal development, a 11 year-old girl (46, XY) with female external genitalia and severe hypertension). CYP17A1 mutations were detected by PCR and direct DNA sequencing in patients and their parents. A homozygous mutation c. 985_987delTACinsAA (p.Y329KfsX418) in Exon 6 was found in patient 1, and a homozygous deletion mutation c. 1459_1467delGACTCTTTC (p.Asp487_Phe489del) in exon 8 in patient 2. The patients manifested with hypertension, hypokalemia, sexual infantilism should be suspected of having 17a-hydroxylase/17,20-lyase deficiency. Definite diagnosis is depended on mutation analysis. Hydrocortisone treatment in time is crucial to prevent severe hypertension and hypokalemia.
Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years.

OBJECTIVES We conducted a prospective, randomized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow's milk allergy. STUDY DESIGN Infants (n = 170) with documented cow's milk allergy were randomly assigned to receive either a soy formula or an extensively hydrolyzed formula. If it was suspected that the formula caused symptoms, a double-blind, placebo-controlled challenge (DBPCFC) with the formula was performed. The children were followed to the age of 2 years, and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years. RESULTS An adverse reaction to the formula was confirmed by challenge in 8 patients (10%; 95% confidence interval, 4.4%-18.8%) randomly assigned to soy formula and in 2 patients (2.2%; 95% confidence interval, 0.3% to 7.8%) randomly assigned to extensively hydrolyzed formula. Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow's milk allergy (11% and 9%, respectively). IgE to soy was detected in only 2 infants with an adverse reaction to soy. Adverse reactions to soy formula were more common in younger (<6 months) than in older (6 to 12 months) infants (5 of 20 vs 3 of 60, respectively, P =.01). CONCLUSIONS Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow's milk allergy. Development of IgE-associated allergy to soy was rare. Soy formula can be recommended as a first-choice alternative for infants >or=6 months of age with cow's milk allergy.
Beyond Open Innovation : the Living Lab Way of ICT Innovation

Open innovation becomes very popular nowadays. However, how to involve users in open innovation process and unleash the potential of more real life end users is still not easy. Living Lab is the development of open innovation paradigm which combines the advantages of users and their real life contexts and provides a structure and governance for involving users. In this paper, we propose a Living Lab process model and methods taxonomy. We evaluate the proposed Living Lab model and methods taxonomy by a Living Lab elderly caring case. Finally, we discuss the implications for ICT innovation and future work.
Membrane proteinase 3 and its interactions within microdomains of neutrophil membranes

Proteinase 3 (PR3) is a serine protease of neutrophil granules released to the medium or into the phagocytic vesicle upon neutrophil stimulation. A fraction of the enzyme is thought to associate with the cell membrane yielding membrane PR3 (mPR3). In autoimmune disorders characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA), the reaction of the latter with their target antigen mPR3 activates the cell inflicting injuries on the surrounding tissues. In a previous communication we provided evidence for the presence of mPR3 in lipid rafts obtained by lysis of neutrophils in Triton X‐100 and for the mediation of PR3 binding to the membrane by a glycosylphosphatidylinositol (GPI)‐anchored neutrophil protein, possibly FcγRIIIb. In the current study we employed the mild detergent Brij 58 to isolate high molecular weight (HMW) protein complexes in the void volume of a Sepharose 4B gel filtration minicolumn. HMW complexes of unstimulated neutrophils comprised PR3, FcγRIIIb, the β2 integrin CD11b/CD18 as well as the membrane and cytosolic subunits of the NADPH oxidase, p22phox and p47phox/p67phox. Treatment of neutrophils with phosphatidylinositol‐specific phospholipase C (PI‐PLC) reduced amounts of PR3 and FcγRIIIb in HMW complexes isolated from the treated cells, supporting our previous suggestion that FcγRIIIb acts as a membrane adaptor for PR3. FcγRIIIb of HMW fractions co‐immunoprecipitated with PR3, indicating their presence in the same protein complex. Since HMW fractions contained also the majority of biotinylated proteins obtained by the reaction of neutrophils with a membrane impermeable biotinylating agent Sulfo‐NHS‐biotin, it was concluded that HMW proteins were derived from cell membranes. Lipid rafts isolated from Brij 58‐lysed neutrophils were similar in their protein composition to the HMW complexes but not identical. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
The Patterns of Music

Young Children • January 2012 ® 2, 3 Research on music and music therapy suggests that math and music are related in the brain from very early in life (Burack 2005). Musical elements such as steady beat, rhythm, melody, and tempo possess inherent mathematical principles such as spatial properties, sequencing, counting, patterning, and one-to-one correspondence. Music also seems to be related to very primal parts of the brain (Hudson 2011). Our bodies cannot help but react physiologically to musical input (Thaut & Kenyon 2003; Hasan & Thaut 2004). This implies that even the youngest children have the potential to inherently respond to music and the mathematical constructs it contains. Recent music neuroscience research indicates that steady beat does affect attention behaviors in humans. We typically process steady beat in the premotor cortex of the brain, an area also related to attention (Bengtsson et al. 2008). Zentner and Eerola (2010) found that 120 infants, ages 5–24 months, were more engaged with rhythm-only stimuli (for example, a steady drum beat) than with speech-only stimuli. The results of this study indicate that children have the potential to be more engaged when listening to steady beats than when listening to verbal-only instructions. Therefore, it is conceivable that listening to a steady beat pattern during mathematics teaching activities in the early childhood classroom could promote better attention and increased engagement in young children. Everyday learning experiences, such as listening to music, are especially important in supporting developing mathematics concepts in children from infancy to 5 years old (Linder, Powers-Costello, & Stegelin 2011). Music is made up of rhythmic patterns and can be structured to make the patterning simple or complex, depending on the activity. Zentner and Eerola (2010) suggest that infants and toddlers have an innate capability to not only see patterns but also hear them in music. Reinforcing these capabilities by teaching patterns through music at an early age may benefit children’s cognitive abilities (Bell et al. 2009; Meltzoff et al. 2009). Teaching patterns to very young children is also a key to the concept of emergent mathematics, which parallels the idea of emergent literacy. As with literacy, emergent mathematics suggests the following:
Environmental context effects in conceptual explicit and implicit memory

Previous research has found environmental context effects for both conceptual explicit and conceptual implicit memory (Parker, Gellatly, & Waterman, 1999). The research presented here challenges these findings on methodological grounds. Experiment 1 assessed the effects of context change on category-exemplar generation (conceptual implicit memory test) and category-cued recall (conceptual explicit memory test). Experiment 2 assessed the effects of context change on word association (conceptual implicit memory test) and word associate cued recall (conceptual explicit memory test). In both experiments, study–test changes in environmental context were found to influence performance only on tests of explicit memory. It is concluded that when retrieval cues across explicit and implicit tests are matched, and the probability of explicit contamination is reduced, then only conceptual explicit test performance is reduced by study–test changes in environmental context.
Microevolution of a Standard Strain ofCryptococcus neoformans Resulting in Differences in Virulence and Other Phenotypes

ABSTRACT Cryptococcus neoformans is a major fungal pathogen for patients with debilitated immune systems. However, no information is available on the stability of virulence or of phenotypes associated with virulence for C. neoformans laboratory strains. A serendipitous observation in our laboratory that one isolate of C. neoformans ATCC 24067 (strain 52D) became attenuated after continuous in vitro culture prompted us to perform a comparative study of nine strain 24067 isolates obtained from six different research laboratories. Each isolate was characterized by DNA typing, virulence for mice, proteinase production, extracellular protein synthesis, melanin synthesis, carbon assimilation pattern, antifungal drug susceptibility, colony morphology, growth rate, agglutination titers, phagocytosis by murine macrophages, capsule size, and capsular polysaccharide structure. All isolates had similar DNA typing patterns consistent with their assignment to the same strain, although minor chromosome size polymorphisms were observed in the electrophoretic karyotypes of two isolates. Several isolates had major differences in phenotypes that may be associated with virulence, including growth rate, capsule size, proteinase production, and melanization. These findings imply that C. neoformans is able to undergo rapid changes in vitro, probably as a result of adaptation to laboratory conditions, and suggest the need for careful attention to storage and maintenance conditions. In summary, our results indicate thatC. neoformans (i) can become attenuated by in vitro culture and (ii) is capable of microevolution in vitro with the emergence of variants exhibiting new genotypic and phenotypic characteristics.
Anal Human Papillomavirus Infection Among Thai Men Who Have Sex With Men With and Without HIV Infection: Prevalence, Incidence, and Persistence

Background: HIV-positive men who have sex with men (MSM) have a higher prevalence of anal human papillomavirus (HPV) infection and anal cancer incidence than HIV-negative MSM. High-risk HPV persistence is an important risk factor for the development of anal cancer. Methods: A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled from the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for HPV genotyping was performed at every visit. HPV prevalence, incidence, clearance, and persistence were calculated. A logistic regression model was used to study factors associated with high-risk HPV persistence. Results: The prevalence of any anal HPV infection was 85% in HIV-positive and 58.5% in HIV-negative MSM (P < 0.0001). The prevalence of high-risk HPV infection was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (P = 0.001). HPV 16 was the most common high-risk HPV type. HIV-positive MSM had a higher prevalence (22.5% vs. 9.8%, P = 0.008) and persistence (16.7% vs. 1.3%, P < 0.001) of HPV 16 than HIV-negative MSM and a trend for higher incidence (16.1 vs. 6.1 episodes/1000 person-months, incidence rate ratio 2.6, P = 0.058). HIV infection (odds ratio: 4.45, 95% confidence interval: 2.11 to 9.4, P < 0.001) and smoking in HIV-positive MSM (odds ratio: 2.3, 95% confidence interval: 1.17 to 4.5, P = 0.015) were independently associated with high-risk HPV persistence in multivariate models. Conclusions: In addition to targeting HIV-positive MSM who are at higher risk for anal, high-risk HPV persistence, anal cancer prevention programs should also integrate behavioral interventions such as smoking cessation to modify risk for high-risk HPV persistence.
Early tumor shrinkage in metastatic colorectal cancer: Retrospective analysis from an irinotecan‐based randomized first‐line trial

Early tumor shrinkage (ETS) has been highlighted as a favorable prognostic factor related to progression‐free survival (PFS) and overall survival (OS) in cytotoxic treatment of metastatic colorectal cancer. Data from a randomized phase III study comparing infusional 5‐fluorouracil plus irinotecan (FUFIRI) versus irinotecan plus oxaliplatin (mIROX) were evaluated. Patient groups were analyzed according to the relative change in maximum tumor diameter between baseline and after 7 weeks of treatment. The ETS cohort was defined as a decrease of ≥20%. Additionally, the non‐ETS cohort was subdivided into “minor shrinkage” (0–19%), “tumor progression” (any increase) and development of “new metastatic lesions”. Progression‐free survival and OS were estimated in all patient subgroups. Assessment of ETS was possible in 201 patients. Early tumor shrinkage was observed in 47% (94/201) and non‐ETS in 53% (107/201) of patients. Patients with ETS had a more favorable outcome with regard to PFS (9.9 months vs 6.1 months, P = 0.029) and OS (27.5 months vs 17.8 months, P = 0.002). In the non‐ETS subgroups, patients with “minor shrinkage” (PFS 8.4 months, OS 21.6 months) showed a markedly better outcome than patients with “early tumor progression” (PFS 4.0 months, OS 15.3 months) or with “new metastatic lesions (PFS 2.2 months, OS 7.6 months). In conclusion, ETS assessment offers accelerated response evaluation when compared to RECIST. In patients treated with chemotherapy alone, ETS ≥20% is associated with excellent outcome. Non‐ETS is a heterogeneous subgroup where patients with minor shrinkage clearly benefit from treatment, and patients with early progression or development of new lesions have an unfavorable prognosis.
A single-base change within the DNA polymerase locus of herpes simplex virus type 2 can confer resistance to aphidicolin

An aphidicolin-resistant (Aphr) mutant of herpes simplex virus (HSV) type 2 strain 186 previously has been shown to induce an altered viral DNA polymerase that is more resistant to aphidicolin and more sensitive to phosphonoacetic acid (PAA) than is wild-type DNA polymerase. In this study the mutation responsible for the aphidicolin-resistant phenotype was physically mapped by marker transfer experiments. The physical map limits for the Aphr mutation were contained in a 1.1-kilobase pair region within the HSV DNA polymerase locus. The 1.1-kilobase-pair fragment of the Aphr mutant also conferred hypersensitivity to PAA, and DNA sequence analysis revealed an AT to GC transition within this fragment of the Aphr mutant. Analysis of the three potential open reading frames within the 1,147-base-pair fragment and comparison with the amino acid sequence of DNA polymerase of HSV type 1 indicated that the Aphr mutant polymerase had an amino acid substitution from a tyrosine to a histidine in the well-conserved region of the DNA polymerase. These results indicate that this single amino acid change can confer altered sensitivity to aphidicolin and PAA and suggest that this region may form a domain that contains the binding sites for substrates, PPi, and aphidicolin.
A new, highly sensitive method for the detection and quantification of penicillin-binding proteins.

A new method for the identification and quantification of penicillin-binding proteins is described which uses fluorescein-coupled penicillins. It allows the rapid detection of 0.2 pmol with the naked eye and 2 fmol with the help of an A.L. F. automatic DNA sequencer. Direct labelling can also be performed on whole bacterial cells.
Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes: Past, present, and future

Glucagon-like peptide-1 (GLP-1)–based therapy improves glycaemic control through multiple mechanisms, with a low risk of hypoglycaemia and the additional benefit of clinically relevant weight loss. Since Starling and Bayliss first proposed the existence of intestinal secretions that stimulate the pancreas, tremendous progress has been made in the area of incretins. As a number of GLP-1 receptor agonists (GLP-1 RAs) continue to become available, physicians will soon face the challenge of selecting the right option customized to their patient's needs. The following discussion, derived from an extensive literature search using the PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide, provides a comprehensive review of existing and upcoming molecules in the GLP-1 RA class in terms of their structure, pharmacological profiles, efficacy, safety, and convenience. Search Methodology: A literature search was conducted using the PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide. Relevant articles were those that discussed structural, pharmacokinetic and pharmacodynamic differences, classification, long-acting and short-acting GLP-1 RAs, phase 3 trials, and expert opinions. Additional targeted searches were conducted on diabetes treatment guidelines and reviews on safety, as well as the American Diabetes Association/European Society for Study of Diabetes (ADA/EASD) statement on pancreatic safety.
A Novel Improved Accuracy Function for Interval Valued Pythagorean Fuzzy Sets and Its Applications in the Decision‐Making Process

The objective of this work is to present an improved accuracy function for the ranking order of interval‐valued Pythagorean fuzzy sets (IVPFSs). Shortcomings of the existing score and accuracy functions in interval‐valued Pythagorean environment have been overcome by the proposed accuracy function. In the proposed function, degree of hesitation between the element of IVPFS has been taken into account during the analysis. Based on it, multicriteria decision‐making method has been proposed for finding the desirable alternative(s). Finally, an illustrative example for solving the decision‐making problem has been presented to demonstrate application of the proposed approach.
Coupled Calcium and Zinc Dyshomeostasis and Oxidative Stress in Cardiac Myocytes and Mitochondria of Rats With Chronic Aldosteronism

A dyshomeostasis of extra- and intracellular Ca2+ and Zn2+ occurs in rats receiving chronic aldosterone/salt treatment (ALDOST). Herein, we hypothesized that the dyshomeostasis of intracellular Ca2+ and Zn2+ is intrinsically coupled that alters the redox state of cardiac myocytes and mitochondria, with Ca2+ serving as a pro-oxidant and Zn2+ as an antioxidant. Toward this end, we harvested hearts from rats receiving 4 weeks of ALDOST alone or cotreatment with either spironolactone (Spiro), an aldosterone receptor antagonist, or amlodipine (Amlod), an L-type Ca2+ channel blocker, and from age/sex-matched untreated controls. In each group, we monitored cardiomyocyte [Ca2+]i and [Zn2+]i and mitochondrial [Ca2+]m and [Zn2+]m; biomarkers of oxidative stress and antioxidant defenses; expression of Zn transporters, Zip1 and ZnT-1; metallothionein-1, a Zn2+-binding protein; and metal response element transcription factor-1, a [Zn2+]i sensor and regulator of antioxidant defenses. Compared with controls, at 4-week ALDOST, we found the following: (a) increased [Ca2+]i and [Zn2+]i, together with increased [Ca2+]m and [Zn2+]m, each of which could be prevented by Spiro and attenuated with Amlod; (b) increased levels of 3-nitrotyrosine and 4-hydroxy-2-nonenal in cardiomyocytes, together with increased H2O2 production, malondialdehyde, and oxidized glutathione in mitochondria that were coincident with increased activities of Cu/Zn superoxide dismutase and glutathione peroxidase; and (c) increased expression of metallothionein-1, Zip1 and ZnT-1, and metal response element transcription factor-1, attenuated by Spiro. Thus, an intrinsically coupled dyshomeostasis of intracellular Ca2+ and Zn2+ occurs in cardiac myocytes and mitochondria in rats receiving ALDOST, where it serves to alter their redox state through a respective induction of oxidative stress and generation of antioxidant defenses. The importance of therapeutic strategies that can uncouple these two divalent cations and modulate their ratio in favor of sustained antioxidant defenses is therefore suggested.
Perspectives of occupational therapists working in primary health promotion.

BACKGROUND/AIM Given a global reorientation of health services towards upstream, or primary health promotion, there is a need to explore the role of occupational therapy in this area of practice. This study aimed to explore and describe the primary health promotion practice of community health workers with an occupational therapy background. The study highlights their practice working at a community or population (macro) level, rather than at the client service (micro) level, and explores related enablers and barriers to this practice. METHODS The study utilised the qualitative methodology of narrative enquiry. Five workers with an occupational therapy background were recruited from community health services within Victoria. Data were gathered via in-depth interviews. Individual participant interview data were ordered to form a narrative detailing each participant's experience. These narratives were then analysed to generate themes representing important aspects of participant's experiences. RESULTS Although some practitioners with an occupational therapy background perform primary health promotion, the findings indicate that a number of barriers deter occupational therapists from engaging in this type of practice, including lack of funding, preparation and limited understanding of the role of occupational therapy in health promotion. Enablers to engagement included undertaking further education, gaining clinical experience and establishing a professional identity. CONCLUSION This study provides insights into the experiences of occupational therapists who work at a macro rather than micro-level of practice, and emphasises some of the barriers and enablers to embracing the sorts of roles that are emerging as part of a changing health system.
Hospital-acquired infections in a burns unit caused by an imported strain of Staphylococcus aureus with unusual multi-resistance

Summary During the past year five patients from countries in the Middle East admitted to a burns unit were found to harbour a strain of Staphylococcus aureus with unusual multi-resistance to antibiotics. The admission of the first patient was followed by an outbreak of infection with this strain involving ten patients in the unit. In addition five staff members were found to be nasal carriers of the strain. As a result of this incident, the following four patients admitted to the unit were isolated on admission and the spread of their strains was thus prevented. It is recommended that patients on admission to burns units, or similar departments with patients very susceptible to infection, are isolated until their bacterial floras have been examined.