Miracle-dz/UniFAR-FTUs huggingface dataset:
Dabigatran for the Treatment and Secondary Prevention of Venous Thromboembolism; A Cost-Effectiveness Analysis for the Netherlands

Background Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting. Methods Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER). Results In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving €1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at €2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at €33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving. Conclusion From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands.
Quantitative Measurement of Split of the Second Heart Sound (S2)

This study proposes a quantitative measurement of split of the second heart sound (S2) based on nonstationary signal decomposition to deal with overlaps and energy modeling of the subcomponents of S2. The second heart sound includes aortic (A2) and pulmonic (P2) closure sounds. However, the split detection is obscured due to A2-P2 overlap and low energy of P2. To identify such split, HVD method is used to decompose the S2 into a number of components while preserving the phase information. Further, A2s and P2s are localized using smoothed pseudo Wigner-Ville distribution followed by reassignment method. Finally, the split is calculated by taking the differences between the means of time indices of A2s and P2s. Experiments on total 33 clips of S2 signals are performed for evaluation of the method. The mean ± standard deviation of the split is 34.7 ± 4.6 ms. The method measures the split efficiently, even when A2-P2 overlap is ≤ 20 ms and the normalized peak temporal ratio of P2 to A2 is low (≥ 0.22). This proposed method thus, demonstrates its robustness by defining split detectability (SDT), the split detection aptness through detecting P2s, by measuring up to 96 percent. Such findings reveal the effectiveness of the method as competent against the other baselines, especially for A2-P2 overlaps and low energy P2.
Protein carbonylation: avoiding pitfalls in the 2,4-dinitrophenylhydrazine assay

Abstract Protein carbonyl content is widely used as both a marker for oxidative stress and a measure of oxidative damage. Widely used methods for determination of protein carbonylation utilize the reaction of carbonyl groups with 2,4-dinitrophenylhydrazine (DNPH) to form protein-bound 2,4-dinitrophenylhydrazones. Hydrazones can be quantitated spectrophotometrically or, for greater sensitivity, detected immunochemically with anti-dinitrophenyl antibodies. Attention to methodology is important to avoid artifactual elevation in protein carbonyl measurements. We studied extracts of Escherichia coli to identify and eliminate such effects. Nucleic acid contamination caused serious artifactual increases in the protein carbonyl content determined by spectrophotometric techniques. Both in vitro synthesized DNA oligonucleotides and purified chromosomal DNA reacted strongly with 2,4-DNPH. Treatment of cell extracts with DNase+RNase or with streptomycin sulfate to precipitate nucleic acids dramatically reduced the apparent carbonyl, while exposure to proteinase K did not. The commercial kit for immunochemical detection of protein carbonylation (OxyBlot™ from Chemicon/Millipore) recommends a high concentration of thiol in the homogenizing buffer. We found this recommendation leads to an artifactual doubling of the protein carbonyl, perhaps due to a thiol-stimulated Fenton reaction. Avoiding oxidizing conditions, removal of nucleic acids, and prompt assay of samples can prevent artifactual effects on protein carbonyl measurements.
Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants.

BACKGROUND Immunosuppression for solid organ transplantation is associated with increased incidence of internal and cutaneous malignant tumors, among which skin cancer is the most common. OBJECTIVE To determine the effects on cutaneous carcinogenesis when stopping therapy with immunosuppressive medications. OBSERVATIONS We followed the clinical course of 6 solid organ transplant recipients after therapy with immunosuppressant medications was stopped because of allograft failure or unacceptable cutaneous carcinogenesis. Generally, we found that stopping therapy with immunosuppressive medications resulted in deceleration of cutaneous carcinogenesis, resolution of cutaneous verrucae vulgaris, and qualitative improvements in skin condition. Four patients experienced marked improvement; 2 did not. CONCLUSIONS Cessation of transplant-associated therapy with immunosuppressive medications for patients in whom cutaneous carcinomas developed after transplantation may lead to deceleration of cutaneous carcinogenesis, decreased verrucae, and improved skin quality within 1 to 2 years. Because of the natural variation in skin cancer development and the small number of cases in this series, definitive conclusions require further study.
Secretome Prediction of Two M. tuberculosis Clinical Isolates Reveals Their High Antigenic Density and Potential Drug Targets

The Excreted/Secreted (ES) proteins play important roles during Mycobacterium tuberculosis invasion, virulence, and survival inside the host and they are a major source of immunogenic proteins. However, the molecular complexity of the bacillus cell wall has made difficult the experimental isolation of the total bacterial ES proteins. Here, we reported the genomes of two Beijing genotype M. tuberculosis clinical isolates obtained from patients from Vietnam (isolate 46) and South Africa (isolate 48). We developed a bioinformatics pipeline to predict their secretomes and observed that ~12% of the genome-encoded proteins are ES, being PE, PE-PGRS, and PPE the most abundant protein domains. Additionally, the Gene Ontology, KEGG pathways and Enzyme Classes annotations supported the expected functions for the secretomes. The ~70% of an experimental secretome compiled from literature was contained in our predicted secretomes, while only the 34–41% of the experimental secretome was contained in the two previously reported secretomes for H37Rv. These results suggest that our bioinformatics pipeline is better to predict a more complete set of ES proteins in M. tuberculosis genomes. The predicted ES proteins showed a significant higher antigenic density measured by Abundance of Antigenic Regions (AAR) value than the non-ES proteins and also compared to random constructed secretomes. Additionally, we predicted the secretomes for H37Rv, H37Ra, and two M. bovis BCG genomes. The antigenic density for BGG and for isolates 46 and 48 was higher than the observed for H37Rv and H37Ra secretomes. In addition, two sets of immunogenic proteins previously reported in patients with tuberculosis also showed a high antigenic density. Interestingly, mice infected with isolate 46 showed a significant lower survival rate than the ones infected with isolate 48 and both survival rates were lower than the one previously reported for the H37Rv in the same murine model. Finally, after a druggability analysis of the secretomes, we found potential drug targets such as cytochrome P450, thiol peroxidase, the Ag85C, and Ribonucleoside Reductase in the secreted proteins that could be used as drug targets for novel treatments against Tuberculosis.
Improved Family of Estimators of Population Mean in Simple Random Sampling

In this paper, a procedure is given for estimating the population mean in simple random sampling without replacement in the presence of auxiliary information. The mean squared error expressions of the proposed estimators have been derived under large sample approximation. We have compared the performances of the proposed estimators with several existing estimators. Both theoretical and empirical findings are encouraging and support the soundness of the proposed procedure for mean estimation.
Nonlinear amplitude dynamics in flagellar beating

The physical basis of flagellar and ciliary beating is a major problem in biology which is still far from completely understood. The fundamental cytoskeleton structure of cilia and flagella is the axoneme, a cylindrical array of microtubule doublets connected by passive cross-linkers and dynein motor proteins. The complex interplay of these elements leads to the generation of self-organized bending waves. Although many mathematical models have been proposed to understand this process, few attempts have been made to assess the role of dyneins on the nonlinear nature of the axoneme. Here, we investigate the nonlinear dynamics of flagella by considering an axonemal sliding control mechanism for dynein activity. This approach unveils the nonlinear selection of the oscillation amplitudes, which are typically either missed or prescribed in mathematical models. The explicit set of nonlinear equations are derived and solved numerically. Our analysis reveals the spatio-temporal dynamics of dynein populations and flagellum shape for different regimes of motor activity, medium viscosity and flagellum elasticity. Unstable modes saturate via the coupling of dynein kinetics and flagellum shape without the need of invoking a nonlinear axonemal response. Hence, our work reveals a novel mechanism for the saturation of unstable modes in axonemal beating.
Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair

Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5′-kinase and DNA 3′-phosphatase activity. To investigate the molecular basis of this disease, we examined the impact of MCSZ mutations on PNKP activity in vitro and in cells. Three of the four mutations currently associated with MCSZ greatly reduce or ablate DNA kinase activity of recombinant PNKP at 30°C (L176F, T424Gfs48X and exon15Δfs4X), but only one of these mutations reduces DNA phosphatase activity under the same conditions (L176F). The fourth mutation (E326K) has little impact on either DNA kinase or DNA phosphatase activity at 30°C, but is less stable than the wild-type enzyme at physiological temperature. Critically, all of the MCSZ mutations identified to date result in ∼10-fold reduced cellular levels of PNKP protein, and reduced rates of chromosomal DNA strand break repair. Together, these data suggest that all four known MCSZ mutations reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5′-kinase activity and all of the mutations greatly reducing cellular DNA 3′-phosphatase activity.
Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective. One additional treatment may be tofacitinib (CP-690,550), an oral inhibitor of Janus kinases 1, 2, and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2, which is expected to block signaling involving gamma chain-containing cytokines including interleukins 2, 4, 7, 9, 15, and 21. These cytokines are integral to lymphocyte activation, function, and proliferation. METHODS In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis. Patients were randomly assigned to receive tofacitinib at a dose of 0.5 mg, 3 mg, 10 mg, or 15 mg or placebo twice daily for 8 weeks. The primary outcome was a clinical response at 8 weeks, defined as an absolute decrease from baseline in the score on the Mayo scoring system for assessment of ulcerative colitis activity (possible score, 0 to 12, with higher scores indicating more severe disease) of 3 or more and a relative decrease from baseline of 30% or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1. RESULTS The primary outcome, clinical response at 8 weeks, occurred in 32%, 48%, 61%, and 78% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.39), 3 mg (P=0.55), 10 mg (P=0.10), and 15 mg (P<0.001), respectively, as compared with 42% of patients receiving placebo. Clinical remission (defined as a Mayo score ≤2, with no subscore >1) at 8 weeks occurred in 13%, 33%, 48%, and 41% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.76), 3 mg (P=0.01), 10 mg (P<0.001), and 15 mg (P<0.001), respectively, as compared with 10% of patients receiving placebo. There was a dose-dependent increase in both low-density and high-density lipoprotein cholesterol. Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500. CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo. (Funded by Pfizer; ClinicalTrials.gov number, NCT00787202.).
The Relationship Between Professional Quality of Life and Caring Ability in Critical Care Nurses

Background: Critical care nursing has some features that may affect the ability of critical care nurses to provide care. Professionals as critical care nurses who deal with peoples’ health and life often experience some levels of stress that affects their quality of life. Objective: This study examined the relationship between professional quality of life and caring ability of critical care nurses. Method: In this descriptive correlational study, 253 critical care nurses working in the medical and surgical intensive care units of Tehran University of Medical Sciences were recruited by convenience sampling method. The data collection tools included demographic data form, Caring Ability Inventory, and questionnaire for professional quality of life version 5. Results: There was a statistically significant positive relationship between the professional quality of life and the caring ability (P < .0001). A significant inverse relationship was found between burn-out subscale of compassion fatigue as one aspect of professional life quality with all 3 aspects of caring ability (knowledge, courage, and patience). Secondary traumatic stress, as another subscale of compassion fatigue (as one aspect of professional quality of life), had no statistically significant correlation with caring ability aspects of knowledge and patience. However, there was a significant inverse correlation between the secondary traumatic stress and courage aspect of caring ability (P < .0001). There was a statistically significant positive relationship between compassion satisfaction aspect of professional life quality with knowledge and patience aspects of caring ability, but there was not any relationship between the compassion satisfaction aspect of professional life quality and the courage aspect of caring ability. Discussion: Improvement of critical care nurses’ professional quality of life may increase their caring ability, thereby leading to better and more effective nursing care. Increased awareness by critical care nurse managers of the compassion fatigue phenomenon (secondary traumatic stress and burnout) and its effect on quality of critical care would be helpful in planning more specific strategies and preventing the onset and progression of these symptoms.
The University of Alabama at Birmingham.

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Modeling User Exposure in Recommendation

Collaborative filtering analyzes user preferences for items (e.g., books, movies, restaurants, academic papers) by exploiting the similarity patterns across users. In implicit feedback settings, all the items, including the ones that a user did not consume, are taken into consideration. But this assumption does not accord with the common sense understanding that users have a limited scope and awareness of items. For example, a user might not have heard of a certain paper, or might live too far away from a restaurant to experience it. In the language of causal analysis (Imbens & Rubin, 2015), the assignment mechanism (i.e., the items that a user is exposed to) is a latent variable that may change for various user/item combinations. In this paper, we propose a new probabilistic approach that directly incorporates user exposure to items into collaborative filtering. The exposure is modeled as a latent variable and the model infers its value from data. In doing so, we recover one of the most successful state-of-the-art approaches as a special case of our model (Hu et al. 2008), and provide a plug-in method for conditioning exposure on various forms of exposure covariates (e.g., topics in text, venue locations). We show that our scalable inference algorithm outperforms existing benchmarks in four different domains both with and without exposure covariates.
FCM parameter estimation methods: Application to infrared spectral histology of human skin cancers

Spectral histology of cancer can be achieved thanks to the analysis of infrared (IR) hyperspectral images. The Fuzzy C-Means (FCM) clustering is particularly well adapted since each object is attributed to all clusters with different membership values. Applied on IR hyperspectral images of human skin cancers, it can highlight fine transitions between tumor and surrounding tissues and/or tumor heterogeneities. However, to provide a biomedically interpretable clustering, the relevant values of the two FCM parameters, i.e. the number of clusters and the fuzziness parameter, must be judiciously selected for each analyzed tissue. In this paper, the performance of some classical cluster validity indices and m-rules previously presented in the literature are evaluated. A new heuristic method based on the redundancy of FCM clusters is also proposed. We show that our method highly improves the clustering quality and computational time when applied on IR images of human skin tumors.
A Novel Human Striated Muscle RING Zinc Finger Protein, SMRZ, Interacts with SMT3b via Its RING Domain*

The RING domain is a conserved zinc finger motif, which serves as a protein-protein interaction interface. Searches of a human heart expressed sequence tag data base for genes encoding the RING domain identified a novel cDNA, named striated muscle RING zinc finger protein (SMRZ). The SMRZ cDNA is 1.9 kilobase pairs in length and encodes a polypeptide of 288 amino acid residues; analysis of the peptide sequence demonstrated an N-terminal RING domain. Fluorescence in situ hybridization localized SMRZ to chromosome 1p33–34. Northern blots demonstrated that SMRZ is expressed exclusively in striated muscle. In the cardiovascular system, SMRZ is more highly expressed in the fetal heart than in the adult heart (slightly higher expression in the ventricle than in the atrium), suggesting that SMRZ is developmentally regulated. SMRZ was found to interact with SMT3b, a ubiquitin-like protein, through the SMRZ-RING domain. This interaction was abolished by mutagenesis of conserved RING domain residues. Transient transfection of SMRZ into C2C12 myoblasts showed localization of SMRZ to the nucleus. These data suggest that SMRZ may play an important role in striated muscle cell embryonic development and perhaps in cell cycle regulation.
Learning Predictive Structures for Semantic Role Labeling of NomBank

This paper presents a novel application of Alternating Structure Optimization (ASO) to the task of Semantic Role Labeling (SRL) of noun predicates in NomBank. ASO is a recently proposed linear multi-task learning algorithm, which extracts the common structures of multiple tasks to improve accuracy, via the use of auxiliary problems. In this paper, we explore a number of different auxiliary problems, and we are able to significantly improve the accuracy of the NomBank SRL task using this approach. To our knowledge, our proposed approach achieves the highest accuracy published to date on the English NomBank SRL task.
Evaluation of the Potency of Kinetin on Radiation Induced Behavioural Changes in Swiss Albino Mice.

INTRODUCTION According to the various independent studies conducted, it is well evident fact that radiation induces oxidative stress in the living system. It is also proved that this oxidative stress will lead to the various behavioural changes such as anxiety and memory impairment. Kinetin is one of the important plant cytokine with anti-aging properties. However, very few studies were conducted to check its potential in ameliorating the behavioural changes induced by the ionizing radiation. AIM This study was aimed to check the potential of kinetin in ameliorating the radiation induced behavioural changes in albino mice. MATERIALS AND METHODS In this study, survival analysis was performed using three different dose of kinetin intervention along with, one radiation control group and one normal control group (n=50). Based on the cumulative survival rate, single effective dose of kinetin was selected and used to evaluate the behavioural changes induced by radiation. The open field apparatus was used to evaluate the anxiety level (n=18, six in each group). Eight armed radial maze was used to evaluate the memory and learning ability in mice model. RESULTS Survival study results suggest 100 mg/kg body weight of kinetin showed highest cumulative survival rate. Therefore, this dose was selected as an effective drug dose for further study. Analysis also showed 6 Gy whole body electron beam radiation had significantly increased anxiety level, increased duration to complete the task as well as mistakes done during the task. Further, kinetin intervention had significantly ameliorated the same. CONCLUSION A 100 mg/kg body weight of kinetin intervention helps in reducing the anxiety and improves the learning ability in mice exposed to electron beam radiation.