Miracle-dz/UniFAR-FTUs huggingface dataset:
The variability in manifestations of untreated patients with phenylketonuria (phenylpyruvic aciduria).

One hundred six cases of phenylketonuria have been surveyed in 11 institutions in New England and Eastern Canada. Data not previously available (and of some degree of uncertainty as to reliability) are presented as to the ages at which patients with phenylketonuria achieve the ability to sit unsupported, to walk independently, and to say recognizable words. A small number of patients achieve these steps at reasonably near the normal age and the degree of variability is such that early developmental timetables should not be overemphasized in interpreting possible effects of any treatment of the disease. Both eczema and seizures are proportionately more frequent in severely retarded patients with phenylketonuria than in those with lesser degrees of intellectual defect. If present at the time an experimental treatment is instituted, they would provide more objective evidence of possible benefit. Electroencephalograms were abnormal in 79% of patients for whom tracings were available and would provide one means of evaluating plans of treatment even in the absence of seizures. While the majority of these patients have blue eyes and blond hair, there is enough evidence to suggest a tendency to darkening of the hair with age that this also should be used with caution in evaluation of treatment. Frequencies of various neurologic manifestations are presented, including unusual hand posturing, tremor, hyperreflexia, clonus and spasticity. These are all variable enough that a reasonably positive diagnosis [See FIG. 2. in Source Pdf. ] by physical examination is not possible, and further, they are not well adapted to evaluation of treatment. The distribution of intelligence quotients in patients with phenylketonuria appears to follow a continuous curve and to include a small number of persons with borderline normal or better intelligence. In assessing the effect of any treatment, it is unwarranted to ascribe to that treatment the attainment of borderline normal intellectual levels that may be reached by small numbers of patients, especially if originally tested in infancy or early childhood. The effect of any therapy can be adequately evaluated only by comparing changes in a number of treated patients with phenylketonuria, with changes in comparable control patients, selected on the basis of intelligence, age, physical accomplishments, and status with respect to hair color, eczema, convulsive seizures and electroencephalographic findings.
Clarifying Vaginal Atrophy’s Impact on Sex and Relationships (CLOSER) survey: emotional and physical impact of vaginal discomfort on North American postmenopausal women and their partners

ObjectiveThis study aims to determine the emotional and physical impact of vaginal atrophy on North American postmenopausal women and their male partners. MethodsA weighted sample of 1,000 married or cohabiting North American postmenopausal women aged 55 to 65 years with vaginal discomfort and 1,000 male partners of postmenopausal women aged 55 to 65 years who experienced vaginal discomfort participated in the Clarifying Vaginal Atrophy’s Impact on Sex and Relationships (CLOSER) online survey to determine the impact of vaginal discomfort and local estrogen therapy on intimacy, relationships, and women’s self-esteem. ResultsVaginal discomfort caused most surveyed North American women to avoid intimacy (58%), experience loss of libido (64%), and experience pain associated with sex (64%). Most surveyed North American men also believed that vaginal discomfort caused their partners to avoid intimacy (78%), experience loss of libido (52%), and find sex painful (59%). Approximately 30% of North American women and men cited vaginal discomfort as the reason they ceased having sex altogether. North American women who used local estrogen therapy to treat their vaginal discomfort reported less painful sex (56%), more satisfying sex (41%), and improved sex life (29%). Most men reported looking forward to having sex (57%) because of their partner’s use of local estrogen therapy. ConclusionsLocal estrogen therapy ameliorates the negative impact of vaginal atrophy on the intimate relationships of North American postmenopausal women and their male partners. Additional education and awareness efforts about the symptoms of and available treatments for vaginal atrophy may be of further benefit to North American partners.
Laboratory testing for HER2/neu in breast carcinoma: an evolving strategy to predict response to targeted therapy.

BACKGROUND Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein. Initial clinical trials used immunohistochemistry (IHC) to test for HER2/neu overexpression in order to select patients for therapy. Fluorescence in situ hybridization (FISH), which tests for gene amplification, is more specific and sensitive than IHC when either assay is compared with HER2/neu overexpression as determined by Northern or Western blot analysis. Many weak overexpressors on IHC testing are not gene amplified on FISH analysis. Such weak overexpressors may be considered false-positives and raise the question of how best to test for HER2/neu. METHODS The literature was surveyed regarding testing for HER2/neu overexpression in breast carcinomas and alternative testing strategies. RESULTS False-positive results are a significant problem when IHC is exclusively used to test for HER2/neu overexpression. The false-positives are overwhelmingly confined to the group of 2+ positives and do not respond to targeted therapy. In contrast, concordance between IHC and FISH is high when immunostaining is interpreted as either negative or strongly positive (3+). Whereas some recent studies have suggested that FISH may better predict response to anti-HER2/neu therapy than IHC, others have indicated that IHC is as effective a predictor as FISH. IHC is less technically demanding and costly than FISH. CONCLUSIONS IHC analysis of HER2/neu in breast carcinoma is a useful predictor of response to therapy with trastuzumab when strongly positive. Negative immunostaining is highly concordant with a lack of gene amplification by FISH. Most weakly positive overexpressors are false-positives on testing with FISH. Thus, screening of breast carcinomas with IHC and confirmation of weakly positive IHC results by FISH is an effective evolving strategy for testing HER2/neu as a predictor of response to targeted therapy.
A Simplification to Support Vector Machine for the Second Training

For complicated recognition problem, the number of support vectors is large and recognition speed is low, because some sample were divided into section by error this time. To solve this problem, a method is bought to simplify the support vector machines based the minimal misestimate margin idea. Experiments show that this new support vector machine not only reduces the number of support vectors and recognition time but also has the same accuracy as (even better than) traditional support vector machine.
Dynamic Channel Feedback Control for Limited-Feedback Multi-User MIMO Systems

Efficient channel feedback methods are becoming more important in limited-feedback multi-user multiple input multiple output (MU-MIMO) systems. We propose a new Dynamic channEl Feedback CONtrol (DEFCON) scheme, which efficiently allocates the limited system resources for channel feedback to appropriate users. The main features of the proposed DEFCON scheme are as follows. Firstly, the channel feedback procedure is composed of two stages: rough channel feedback of all users and additional precise channel feedback of the selected users only. Secondly, each selected user is allocated with different amount of resources for additional channel feedback according to its channel status. We mathematically solve the resource allocation problem by proposing a suboptimal method, which utilizes convex optimization technique combined with iterative steepest decent direction search algorithm. Numerical results show that zero-forcing beamforming (ZFBF) with the proposed DEFCON scheme considerably outperforms previous limited-feedback MU-MIMO schemes such as ZFBF with conventional static feedback method and per user unitary beamforming rate control (PU2RC).
Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions Demonstrate Equal Effectiveness in Preventing Cellular Edema in Preserved Human Pancreata Intended for Islet Isolation

We have previously reported that both Histidine-Tryptophan-Ketoglutarate solution (HTK) and University of Wisconsin solution (UW) provide equal preservation of the pancreas for islet isolation, based upon the assessment of islet yield and function. In this study, we further assessed the ability of each solution to prevent cellular edema. This large-scale, retrospective analysis included the assessment of islet isolation outcomes influenced by cellular edema, such as pancreatic digestion efficacy, purification outcome, and islet size distribution. Multi-variable linear regression analysis, adjusted for donor age, sex, BMI, cold ischemia time, and enzyme, demonstrated similar results for the HTK group (n = 95) and the UW group (n = 157), including post-purification islet yields (the HTK: 289,702 vs. the UW: 283,036; p = 0.76), percentage of digested pancreatic tissue (the HTK: 66.9% vs. the UW: 64.1%; p = 0.18), and islet loss from post-digestion to post-purification (the HTK: 24,972 vs. the UW: 39,551; p = 0.38). Changes in islet size between the post-digestion and post-purification stages were comparable within each islet size category for the HTK and the UW groups (p = 0.14 0.99). Tissue volume distribution across purification fractions and islet purity in the top fractions were similar between the groups; however, the HTK group had significantly higher islet purity in the middle fractions (p = 0.003 0.008). Islet viability and stimulation indices were also similar between the HTK and the UW groups. In addition, we analyzed a small sample of patients transplanted either with HTK (n = 7) or UW (n = 8) preserved islets and found similar outcomes. This study demonstrates that HTK and UW solutions offer comparable pancreas preservation and are equally efficacious in the prevention of pancreatic tissue edema in islet transplantation. Future studies assessing in vivo islet outcomes in larger samples are needed for complete analysis of the effects of HTK on islet transplantation.
Idea management in creative lives

This research explores how ideas occur in creative work and the strategies and tools used to represent and develop them. We describe the analysis of an open questionnaire survey of creative practitioners' use of devices to represent ideas and capture inspirational material. Unconscious processes, novel experiences and time away from practice frequently provoke ideas. Our analysis finds that ubiquitous devices are important to practitioners for making initial representations for personal use. Paper and pen remains by far the most common device employed, however respondents perceived organisational advantages in new technology. Representations are created as initial memory aids, platforms for development, or to share ideas. A single representation is rarely suitable for all these purposes.
Effect of Multipurpose Solutions on Cell Morphology and Cytokine Production by Corneal Epithelial Cells

Purpose. We sought to determine whether human corneal limbal epithelial cells (HCLE) differ in their physiological response and production of inflammatory mediators during exposure to two multipurpose disinfecting solutions that differ in only four excipients. Methods. HCLE were exposed to dilutions (1%–20%) of OPTI-FREE Express and OPTI-FREE RepleniSH for 2, 6, or 18 h. Cell numbers were measured using CyQuant and metabolic activity assays. Morphology, viability, and apoptotic changes were examined by confocal microscopy after staining with Calcein AM/propidium iodide or Hoechst 33,342/propidiun iodide/YO-PRO-1. Cytokine responses and arachidonic acid metabolites were examined by enzyme-linked immunosorbent assay. Results. OPTI-FREE Express showed greater reductions in corneal cell metabolic activity (up to 3-fold) than OPTI-FREE RepleniSH over 18 h. Cells exposed to OPTI-FREE Express were highly vacuolated, whereas those exposed to OPTI-FREE RepleniSH had morphology consistent with a presumed apoptotic response. OPTI-FREE Express elicited higher levels of interleukin (IL)-6 (maximum 4225 ± 300 pg/mL) and IL-8 (maximum 1094 ± 250 pg/mL) from cells than OPTI-FREE RepleniSH (maximum of 1717 ± 225 pg/mL and 930 ± 300 pg/mL, respectively) at all concentrations tested after 18 h. HCLE did not produce leukotriene B4 or prostaglandin E2 on stimulation, and IL-1&bgr; was produced in low levels, but its production was not different between multipurpose disinfecting solution types. Conclusions. The findings reported here are the first to describe the pattern of cytokine production produced in corneal epithelial cells in response to contact lens solutions. Alteration of only four excipients in the formulations had such effects on corneal epithelia; however, these differences do not explain differences in the incidences of corneal infiltrative events between these solutions. This might indicate that changes in the rates of infiltrative events result from interactions of the solutions with the contact lens surface, or directly with the corneal immune system, or as the result of gram-negative contamination of lens cases.
Risk Factors for Developing Avascular Filtering Bleb After Fornix-based Trabeculectomy With Mitomycin C

PurposeTo investigate risk factors for developing avascular filtering blebs after primary fornix-based trabeculectomy with mitomycin C (MMC). MethodsOne-year observational case series. Ninety eyes of 90 patients who underwent primary trabeculectomy with MMC and a fornix-based conjunctival flap were examined. The appearance of the filtering bleb was classified at the last examination into 2 groups: vascular bleb or avascular bleb. Potential predictors that were entered into the model were age at surgery, sex, glaucoma diagnosis, preoperative intraocular pressure (IOP), number of antiglaucoma medications before surgery, use of topical steroid before surgery, duration of MMC application, laser suturolysis, excessive filtration, combination with cataract surgery, and needling revision. IOP was evaluated at 6 and 12 months postoperatively. ResultsAvascular blebs were seen in 28 eyes (31%) at 12 months. Logistic regression analysis revealed that the risk factors for developing avascular blebs after primary fornix-based trabeculectomy included secondary glaucoma [odds ratio (OR)=3.927, P=0.015], excessive filtration (OR=3.215, P=0.043), and not performing laser suturolysis after trabeculectomy (OR=3.597, P=0.031). The mean IOP was decreased from 30.3±13.4 mm Hg to 8.8±3.9 mm Hg in the avascular bleb group and from 24.6±9.9 mm Hg to 10.5±3.3 mm Hg in the vascular bleb group at 12 months (P<0.01, both groups, paired t test). ConclusionsSecondary glaucoma, excessive filtration, and no performance of laser suturolysis after trabeculectomy might be risk factors for development of avascular filtering blebs in primary fornix-based trabeculectomy.
Therapy with immunoglobulin suppresses myocarditis in a murine coxsackievirus B3 model. Antiviral and anti-inflammatory effects.

BACKGROUND The treatment of some inflammatory diseases (eg, Kawasaki disease) with immunoglobulin has been demonstrated to be effective. Accordingly, to elucidate the mechanism underlying such actions of immunoglobulin, we examined its effects on murine coxsackievirus B3 (CB3) myocarditis. METHODS AND RESULTS An in vitro study showed dose-dependent suppression of CB3 by immunoglobulin. Immunoglobulin 1 g.kg-1.d-1 IP was administered to CB3-infected C3H/He mice daily for 2 weeks, beginning simultaneously with virus inoculation in experiment 1 and on day 14 after virus inoculation in experiment 2. In both experiments, survival was higher in treated than in control mice; at the time of death, inflammatory also were reduced. Notably, in experiment 1, immunoglobulin administration completely suppressed the development of myocarditis. Serum-neutralizing antibody titers in the treated mice were significantly higher than those in untreated mice in experiment 1 but not in experiment 2. The circulating antibodies of the treated mice were primarily of exogenous origin in experiment 1 and of exogenous and endogenous origins in experiment 2. The analysis of splenic lymphocyte subsets revealed a marked decrease of the B cell population in the treated mice. CONCLUSIONS Immunoglobulin therapy completely suppressed acute CB3 myocarditis by transferring the neutralizing antibody into the host in the acute viremic stage and induced an anti-inflammatory effect in the subsequent aviremic stage; the reduction of the splenic B-cell population may be closely associated with an anti-inflammatory effect.
Assessment and control of VOCs emitted from gas stations in Tehran, Iran

In this research, gasoline vapours including Benzene, Toluene, Xylene (BTX) and Total Volatile Organic Compounds (TVOCs) emitted from vent pipes of underground storage tanks (USTs) were measured at six gas stations in Tehran. Thereafter, gas station No. 29 was selected as a pilot station and equipped with a vapour control system. The vapours were measured during the summer of 2013 and winter of 2014 in two states, before and at the time of gasoline discharge from a petrol tanker to the UST. The results reveal that the average of BTX and TVOCs are 161.22, 200.81, 229 and 647.01 ppm, respectively, higher than the World Health Organisation (WHO) guidelines. The average of TVOCs and BTX in the situation in which the control system is inactive at the pilot station, are 259.13, 55.9, 73.03 and 96.88 ppm, respectively. After activating the control system at the pilot station, the VOCs were reduced by 0.01 ppm. Almost 99.99% control was obtained for this system and 87% of the people living around the pilot station were satisfied and no longer had any complaints about the bad odour of VOCs. It can be concluded that gasoline discharge from the petrol tanker to UST, is the main reason behind the overproduction of VOCs in Tehran's gas stations (P<0.001). So, the most important element is to reduce VOCs at Tehran's gas stations by installing a vapour control systems in all the stations and activating the systems at the time of gasoline discharge.
Modified lateral positioned flap with platelet-rich fibrin graft for treatment of denuded root surfaces: A clinical study

Background: Root coverage (RC) procedures such as lateral positioned flap (LPF) have been used since long time but with limited success and specific indications. Aim: This prospective clinical study was designed to evaluate clinically the effect of modified LPF (mLPF) with platelet-rich fibrin (PRF) graft for the treatment of denuded root surfaces. Materials and Methods: Fifteen isolated Miller's Class I and II gingival recession of single-rooted teeth were selected for the study. Scaling and root planing was done, and oral hygiene instructions were given to the patients. Plaque index, gingival index, and recession parameters (probing depth, gingival recession height, clinical attachment level [CAL], and width of keratinized tissue [WKT]) were assessed at baseline. Following this, mLPF with PRF was done at the recession sites, and parameters were assessed at 3 and 6 months. Statistical Analysis: To analyze the posttreatment effect, paired t-test was performed at relevant degrees of freedom and 95% confidence level. Results: The mean percentage of RC attained was 72.2% at 3 months and 73.5% at 6 months. The WKT shows a mean gain of 2.93 mm at 3 months and 3 mm at 6 months. Conclusion: mLPF with PRF produced statistically significant reduction in recession depth and gain in both CAL and WKT by the end of 6 months.
Prevention of Apoptosis as a Possible Mechanism behind Improved Cryoprotection of Hematopoietic Cells by Catalase and Trehalose

Background. Our previous in vitro work has shown the usefulness of membrane stabilizers and antioxidants as additives in conventional freezing medium to freeze mouse and human hematopoietic cells. The present work was carried out using murine model to test the in vivo engraftment ability of mouse bone marrow frozen with (test cells) or without (control cells) addition of a combination of trehalose and catalase in the medium containing 10% dimethyl sulfoxide (DMSO). Methods. Viability, nucleated cell recovery, and progenitor content of revived cells were measured. Freezing efficacy was tested by in vivo assays like colony forming unit-spleen (CFU-S), pre-CFU-S, and short-term engraftment of frozen marrow in irradiated mice. Long-term engraftment ability of frozen marrow was assessed using a Ly5.1-Ly 5.2 chimera model. Levels of apoptosis and reactive oxygen species (ROS) generated in revived cells were estimated. The former by Annnexin V, TUNEL, and DNA laddering and the latter by DCFH-DA probe. Results. Our results show that the combination of catalase and trehalose with 10% DMSO improves freezing efficacy not only in terms of viability, cell recovery, and progenitor content but also by in vivo assays like CFU-S, pre-CFU-S, and short- and long-term engraftment. Both the level of apoptosis and ROS generation were considerably reduced in test set as compared to control set. Conclusions. We conclude that inclusion of a combination of trehalose and catalase in conventional freezing medium leads to enhanced engraftment potential of cryopreserved mouse bone marrow cells probably by preventing apoptotic cell death. Our observation using animal model may have significant clinical implications.
Membrane Active Arginine and Tryptophan Rich Peptides

Genetic diseases, cancer and antibiotic resistant bacterial infections are causing many people a great deal of suffering every year. Treatment and cure of these medical conditions are desirable, but also challenging for the medical industry. Membrane-active peptides (MAPs) are a group of peptides that are very promising for all these medical applications. These peptides include the cell-penetrating peptides (CPPs) which have the ability to efficiently transport DNA, proteins and other macromolecules into cells, and the antimicrobial peptides (AMPs) that can kill or inhibit the growth of bacteria, fungi and parasites. The properties of these peptides are overlapping, and have been suggested to depend on both the peptide sequence and membrane constituents. The mechanisms of action of these peptides are, however, not yet fully understood. The goal with the work presented in this thesis, therefore is to better understand the mechanistic details of how membrane-active peptides bind to and interact with cellular membranes. The work focuses on the influence of the amino acids arginine and tryptophan on peptide function and membrane interaction, which has been investigated using cellular and physicochemical studies. The results from the work in this thesis indicate that the number and position of the amino acid tryptophan in the peptide sequence affect both cellular uptake and antibacterial properties. The biological effect seems partly related to the secondary structure of the peptides and the composition of the lipid membrane. The results also show that cellular uptake gains from increasing arginine content, and that proteoglycans at the cell surface specifically affect the cellular uptake of arginine-rich peptides. In addition, it is shown that the properties of the peptides may be affected by fluorescent labeling, and that this effect depends on the peptide amino acid sequence. In summary, these results give further information about how specific amino acids may affect the properties of the peptide, and how this regulates both membrane function and membrane specificity of membrane-active peptides.