Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Predicted Scaffold-Compatible Sequence Variation in the Triple-Hairpin Structure of Human Immunodeficiency Virus Type 1 gp41 with Patient Data

ABSTRACT It has been proposed that the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 (e-gp41), involved in HIV entry into the target cell, exists in at least two conformations, a pre-hairpin intermediate and a fusion-active hairpin structure. To obtain more information on the structure-sequence relationship in e-gp41, we performed in silico a full single-amino-acid substitution analysis, resulting in a Fold Compatible Database (FCD) for each conformation. The FCD contains for each residue position in a given protein a list of values assessing the energetic compatibility (ECO) of each of the 20 natural amino acids at that position. Our results suggest that FCD predictions are in good agreement with the sequence variation observed for well-validated e-gp41 sequences. The data show that at a minECO threshold value of 5 kcal/mol, about 90% of the observed patient sequence variation is encompassed by the FCD predictions. Some inconsistent FCD predictions at N-helix positions packing against residues of the C helix suggest that packing of both peptides may involve some flexibility and may be attributed to an altered orientation of the C-helical domain versus the N-helical region. The permissiveness of sequence variation in the C helices is in agreement with FCD predictions. Comparison of N-core and triple-hairpin FCDs suggests that the N helices may impose more constraints on sequence variation than the C helices. Although the observed sequences of e-gp41 contain many multiple mutations, our method, which is based on single-point mutations, can predict the natural sequence variability of e-gp41 very well.
The Fluid Study Protocol: A Randomized Controlled Study on the Effects of Bioimpedance Analysis and Vitamin D on Left Ventricular Mass in Peritoneal Dialysis Patients

♦ Objectives: We will evaluate the effects of bioimpedance analysis–guided fluid management to reduce volume expansion, of vitamin D3 supplementation, and of the combination of those techniques on decrease of left ventricular mass in peritoneal dialysis (PD) patients. ♦ Design: This multicenter randomized controlled trial, with a 2×2 factorial design, will be conducted at PD clinics affiliated with 3 Canadian teaching hospitals. Consenting PD patients 18 years of age or older will be included. Patients will be excluded if they have contraindications to bioimpedance or magnetic resonance imaging, life or technique expectancy of less than 1 year, peritonitis within the preceding 3 months, or serum calcium above 2.55 mmol/L. ♦ Intervention: The study will randomize 70 patients to bio-impedance–guided volume management or to usual care and to vitamin D3 50,000 U weekly for 8 doses, and then 10,000 U weekly or to matching placebo. ♦ Main Outcome Measures: The primary outcome will be change in left ventricular mass at 1 year as determined by cardiac magnetic resonance imaging. The secondary outcome will be a composite endpoint of death, nonfatal cardiovascular event, and transfer to hemodialysis for dialysis inadequacy or ultrafiltration failure. Other outcome measures will include blood pressure, quality of life, 6-minute walk test, inflammatory and fibrotic markers and their association with peritoneal membrane transport properties, and residual renal function. Patients will be followed for clinical outcomes for up to 3 years. ♦ Conclusions: This study will assess whether bioimpedance-directed volume management and vitamin D3 supplementation can improve left ventricular mass in PD patients.
Applying of Hierarchical Clustering to Analysis of Protein Patterns in the Human Cancer-Associated Liver

Background There are two ways that statistical methods can learn from biomedical data. One way is to learn classifiers to identify diseases and to predict outcomes using the training dataset with established diagnosis for each sample. When the training dataset is not available the task can be to mine for presence of meaningful groups (clusters) of samples and to explore underlying data structure (unsupervised learning). Results We investigated the proteomic profiles of the cytosolic fraction of human liver samples using two-dimensional electrophoresis (2DE). Samples were resected upon surgical treatment of hepatic metastases in colorectal cancer. Unsupervised hierarchical clustering of 2DE gel images (n = 18) revealed a pair of clusters, containing 11 and 7 samples. Previously we used the same specimens to measure biochemical profiles based on cytochrome P450-dependent enzymatic activities and also found that samples were clearly divided into two well-separated groups by cluster analysis. It turned out that groups by enzyme activity almost perfectly match to the groups identified from proteomic data. Of the 271 reproducible spots on our 2DE gels, we selected 15 to distinguish the human liver cytosolic clusters. Using MALDI-TOF peptide mass fingerprinting, we identified 12 proteins for the selected spots, including known cancer-associated species. Conclusions/Significance Our results highlight the importance of hierarchical cluster analysis of proteomic data, and showed concordance between results of biochemical and proteomic approaches. Grouping of the human liver samples and/or patients into differing clusters may provide insights into possible molecular mechanism of drug metabolism and creates a rationale for personalized treatment.
Transfusion of blood during cardiac surgery is associated with higher long-term mortality in low-risk patients.

OBJECTIVE Numerous reports have emphasized the need for reduction in transfusions of allogeneic red blood cells (RBC) due to increased morbidity and mortality. Nevertheless, transfusion rates are still high in several cardiac surgery institutions. Reports on long-term survival after cardiac surgery and RBC transfusion are few. METHODS Data from the Western Denmark Heart Registry (WDHR) were used to identify all (25,117) adult cardiac surgery performed in four centres during 1999-2010. Patients with multiple entries (1049), re-do cardiac surgery (985), special/complex procedures (2329), dying within 30 days (668) and not eligible for follow-up (85) were excluded leaving a cohort of 20,001. Registration in the WDHR is mandatory. WDHR and the unique Danish Civil Registration System with continuous sequential updates of the Danish population ensure that all patients and outcomes are accounted for. RESULTS Kaplan-Meier survival plot for low-risk patients (EuroSCORE 0-4), undergoing simple cardiac surgery showed a significantly lower estimated survival after >4500 days (0.637 vs. 0.745) when receiving perioperative RBC transfusion (P<0.0001). The difference was less evident in patients with EuroSCORE 5-9 (0.373 vs. 0.4436, P<0.0001), while high-risk patients showed no difference. Adjusted risk ratio, after RBC transfusion, containing among others age, sex, EuroSCORE and diabetes, was 1.83 (95% CI (confidence interval) 1.67-2.01). The survival rate was independent of up till six units of RBC. CONCLUSION Long-term follow-up of low-risk patients undergoing simple cardiac surgery demonstrates a more than 10% higher mortality when receiving perioperative RBC transfusion. Even transfusion of 1-2 units seems to carry a risk of that magnitude.
Characterization of cytokine production in infectious mononucleosis studied at a single‐cell level in tonsil and peripheral blood

Cytokine profile and production was studied at a single‐cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine‐specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL‐1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL‐2, interferon‐gamma (IFN‐γ), IL‐4, IL‐5, IL‐6, IL‐10, GM‐CSF, tumour necrosis factor‐alpha (TNF‐α) or TNF‐β, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti‐CD3 MoAbs for 2–3 h restimulalion under conditions which did not activate normal cells. By this approach 168±120 cells/10000 peripheral blood mononuclear cells produced IFN‐γ as compared with 10±8 cells/10000 non‐stimulated cultured cells obtained from IM patients (P < 0.001) and 1 /10000 cells obtained from healthy controls, respectively. No induced production of IL‐2, IL‐3, IL‐4, IL‐5, IL‐10, GM‐CSF or TNF‐β was detected in IM cells obtained from peripheral blood by this restimulalion. In contrast, a spontaneous cylokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160±40 cells/10000 cells produced IL‐2, 40±30 cells IL‐6. 30±30 cells TNF‐β and 35±25 cells IFN‐γ, respectively. No such spontaneous IL‐2, IL‐6, TNF‐γ or IFN‐γ production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.
Maximizing the Fair Allocation of Opportunistic Spectrum for CR Ad Hoc Networks

Cognitive Radios (CRs) address spectrum scarcity and under-utilization of the spectrum. Allocating spectrum to CR nodes in a network is neither easy nor straight-forward since spectrum availability is space and time-varying. The Link layer always sets up communication between nodes in a CR ad hoc network by allocating the available spectrum suitably. In a time-slotted model, allocation of channels amongst CR nodes is a NP complete problem. Moreover, since the availability of spectrum is time varying, all the nodes in the network may not be allocated sufficient resources. Thus there is always a possibility that a node may starve compared to its counterparts. In this article, we address the issue of fairness in a CR ad hoc network and propose novel distributed heuristics to allocate spectrum fairly. In literature, max-min, max-sum and max-proportional fairness based schemes are proposed to provide fairness in these CR ad hoc networks. We compare our heuristic results with these schemes, and discuss why our method is significantly better.
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease

We previously reported age of onset (AOO) modifier genes in the world's largest pedigree segregating early-onset Alzheimer's disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10−4, P FDR = 9.34 × 10−3) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10−3, P FDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, P FDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of AD.
ISOLATION AND SCREENING OF L-ASPARAGINASE PRODUCING FUNGI FROM SOIL SAMPLES Research Article

L-asparaginase has been used as anti-tumor agent for the effective treatment of acute lymphoblastic leukemia and as food processing aid to reduce the acrylamide formation during frying of starchy foods at high temperature. In the present study thirty eight fungal strains were isolated from soils which collected from different parts of India. The isolated fungi were screened for L-asparaginase production using Czapek’s agar media. On the basis of pink colour zone formed, one fungal strain was selected and identified as Aspergillus sp (KUFS20). A comparative study was carried out to evaluate L-asparaginase production in submerged and solid state fermentation using different substrates. Among the twenty substrates used, orange peel (70.67±1.14 U/g) showed maximum enzyme production.
Taurine and Epidermal Growth Factor Belong to the Signature of First-Episode Psychosis

This study evaluated the levels of two amino acid derivatives taurine and spermine in first-episode psychosis (FEP) patients and their response to antipsychotic treatment. The levels of taurine and spermine were significantly up-regulated in antipsychotic-naïve FEP patients compared to control subjects (CS). Treatment of FEP patients with antipsychotic drugs significantly reduced the positive symptoms of schizophrenia. This positive effect was accompanied by a significant reduction of taurine and spermine to the levels measured in CS. General linear model was used to establish associations of taurine and spermine with the levels of cytokines and growth factors, measured in our previous experiments using the same study sample. There was a strong association between taurine and epidermal growth factor (EGF). Both biomarkers significantly correlated with the disease symptoms as well as with the effectiveness of antipsychotic treatment. Accordingly one can conclude that taurine and EGF belong to the signature of FEP. Most probably they reflect altered oxidative stress and corrupted function of N-methyl-D-aspartate (NMDA) receptors in FEP.
A Decomposition-Based Approach to Reasoning about Free Space Path-Connectivity for Rigid Objects in 2D

In this paper, we compute a conservative approximation of the path-connected components of the free space of a rigid object in a 2D workspace in order to solve two closely related problems: to determine whether there exists a collision-free path between two given configurations, and to verify whether an object can escape arbitrarily far from its initial configuration -- i.e., whether the object is caged. Furthermore, we consider two quantitative characteristics of the free space: the volume of path-connected components and the width of narrow passages. To address these problems, we decompose the configuration space into a set of two-dimensional slices, approximate them as two-dimensional alpha-complexes, and then study the relations between them. This significantly reduces the computational complexity compared to a direct approximation of the free space. We implement our algorithm and run experiments in a three-dimensional configuration space of a simple object showing runtime of less than 2 seconds.
Decreased Lymphocyte-to-Monocyte Ratio Predicts Poor Prognosis of Acute Ischemic Stroke Treated with Thrombolysis

Background Our previous study found that lower lymphocyte-to-monocyte ratio (LMR) is an independent risk factor of clinical outcome of acute ischemic stroke (AIS). However, whether lower LMR is independently associated with adverse prognosis of AIS treated with thrombolysis has not been determined. In this study, we explored the relationship between LMR and prognosis of AIS treated with thrombolysis. Material/Methods We retrospectively enrolled 108 patients treated with thrombolysis. LMR was calculated according to lymphocyte count and monocyte count on admission. Patients were classified into 3 groups according to LMR values on admission (group 1 LMR >4.34, group 2 LMR 2.79 to 4.34, group 3 LMR <2.79). Neurologic impairment was estimated by use of the National Institute of Health Stroke Scale. Clinical prognosis at 3 months was assessed by modified Rankin Scale. The relationship between LMR and neurologic impairment was analyzed by Spearman rank correlation. Receiver operating characteristic curve (ROC) was used to evaluate the ability of LMR to predict outcome. Results Patients in group 3 had lower lymphocyte counts and LMR values and higher monocyte counts (P<0.001). LMR value was negatively correlated with the degree of neurologic impairment (r=−0.372, P<0.001). The ROC suggested a moderate sensitivity (71.6%) and specificity (80.5%) of LMR for predicting prognosis with an optimal cut-off point at 3.48. Higher LMR value was an independent protective factor against adverse prognosis (odds ratio 0.683, 95% confidence interval 0.490−0.952, P=0.024). Conclusions A lower LMR value is an independent predictor of poor prognosis of AIS treated with thrombolytic therapy.
Mapping Atheroprotective Functions and Related Proteins/Lipoproteins in Size Fractionated Human Plasma *

HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS). Each fraction was evaluated for its proteomic content as well as its ability to promote cholesterol efflux and protect low density lipoprotein (LDL) from free radical oxidation. For each function, several peaks of activity were identified across the plasma size gradient. Neither cholesterol efflux or LDL antioxidation activity correlated strongly with any single protein across the fractions. However, we identified multiple proteins that had strong correlations (r values >0.7, p < 0.01) with individual peaks of activity. These proteins fell into diverse functional categories, including those traditionally associated with lipid metabolism, as well as alternative complement cascade, innate immunity and clotting cascades and immunoglobulins. Additionally, the phospholipid and cholesterol concentration of the fractions correlated strongly with cholesterol efflux (r = 0.95 and 0.82 respectively), whereas the total protein content of the fractions correlated best with antioxidant activity across all fractions (r = 0.746). Furthermore, two previously postulated subspecies (apoA-I, apoA-II and apoC-1; as well as apoA-I, apoC-I and apoJ) were found to have strong correlations with both cholesterol efflux and antioxidation activity. Up till now, very little has been known about how lipoprotein composition mediates functions like cholesterol efflux and antioxidation.
Effect of Educational Instructions on Mothers’ Self-Efficacy Regarding Quality of Life for their Children with Congenital Heart Diseases

Background : Children with congenital heart diseases face serious problems which affect the quality of their life so; promoting mothers’ self-efficacy may affect quality of life of their children with congenital heart disease. The study aimed to evaluate the effect of educational instructions on mothers’ self-efficacy regarding quality of life their children with congenital heart diseases. Design: A quasi-experimental research design was used in the present study; the study was conducted at inpatient and outpatient Pediatric Department of Tanta Main University Hospital which affiliated to Ministry of Higher Education and scientific Research and Kafer El-Shiek Main University Hospitals. Subjects and Method: a purposive sample of seventy children and their mothers were involved in the present study the children aged from six to twelve years old. Three Tools were used: Mothers’ knowledge structured questionnaire, the children’s quality of life scale and the mothers’ self-efficacy scale. The results revealed that mothers’ knowledge had improved after the educational instructions implementation with positive correlation between total mothers knowledge about congenital heart diseases and their self-efficacy which in turn improve the quality of life of their children. The study concluded that the educational instructions had great effect in improving mothers’ knowledge, self-efficacy and quality of life of their children with congenital heart diseases. The study recommended that periodical educational program should be conducted for nurses to be knowledgeable about congenital heart diseases and nursing caring of these children.
Patient safety incidents – what to do after the event

Background:Following a patient safety incident, patients and families need disclosure and reconciliation, practitioners need debriefing, and the organization needs to implement changes to prevent further errors. In order to substantiate the Canadian Incident Analysis Framework, the Canadian Patient Safety Institute (CPSI) invited Queen's Joanna Briggs Collaboration (QJBC) to work collaboratively with them to provide a synthesis of the current literature on the frameworks, models or tools that address patient safety incident management. Objective:To perform a mapping review of the international literature focused on frameworks, models or tools for patient safety incident management across the continuum of care. Methods:We followed Joanna Briggs Institute method of synthesis. A 3-step approach was used to search the peer-review literature: 1) initial search of MEDLINE and CINAHL; 2) detailed search across all databases using all keywords and index terms; 3) hand search the reference lists of includedpapersto locate additional studies. Targeted databases included: CINAHL; Medline; EMBASE; PsycINFO; AMED; Cochrane; Web of Science, Ageline; GlobalHealth; and Social Sciences Abstracts. Search strategies were tested for sensitivity and specificity by QJBC Library Scientist using the Peer Review of Electronic Search Strategies (PRESS) methodology developed by Canadian Agency for Drugs and Technologies in Health. Results:The search located 4,413 citations that provided 21 papers. Publication dates spanned 1999–2012 and included 10 theoretical papers, seven descriptive studies, three reviews, and one qualitative study. Thirteen models, four frameworks and four tools were identified. Discussion:A range of approaches were described including psychological and cognitive frameworks, statistical models, and human factors approaches. Only one model had been formally evaluated and implemented in several settings. Conclusion:To advance our knowledge in this area existing models, frameworks and tools need to be evaluated and implemented. Further research would be beneficial.