Miracle-dz/UniFAR-FTUs huggingface dataset:
Bevacizumab beyond disease progression after first‐line treatment with bevacizumab plus chemotherapy in advanced nonsquamous non–small cell lung cancer (West Japan Oncology Group 5910L): An open‐label, randomized, phase 2 trial

Bevacizumab combined with platinum‐based chemotherapy has been established as a standard treatment option in the first‐line setting for advanced nonsquamous non–small cell lung cancer (NSCLC). However, there has been no evidence to support the use of bevacizumab beyond disease progression in such patients.
A Definition for Hesitant fuzzy Partitions

AbstractIn this paper, we define hesitant fuzzy partitions (H-fuzzy partitions) to consider the results of standard fuzzy clustering family (e.g. fuzzy c-means and intuitionistic fuzzy c-means). We define a method to construct H-fuzzy partitions from a set of fuzzy clusters obtained from several executions of fuzzy clustering algorithms with various initialization of their parameters. Our purpose is to consider some local optimal solutions to find a global optimal solution also letting the user to consider various reliable membership values and cluster centers to evaluate her/his problem using different cluster validity indices.
Expression Quantitative Trait Loci Information Improves Predictive Modeling of Disease Relevance of Non-Coding Genetic Variation

Disease-associated loci identified through genome-wide association studies (GWAS) frequently localize to non-coding sequence. We and others have demonstrated strong enrichment of such single nucleotide polymorphisms (SNPs) for expression quantitative trait loci (eQTLs), supporting an important role for regulatory genetic variation in complex disease pathogenesis. Herein we describe our initial efforts to develop a predictive model of disease-associated variants leveraging eQTL information. We first catalogued cis-acting eQTLs (SNPs within 100kb of target gene transcripts) by meta-analyzing four studies of three blood-derived tissues (n = 586). At a false discovery rate < 5%, we mapped eQTLs for 6,535 genes; these were enriched for disease-associated genes (P < 10−04), particularly those related to immune diseases and metabolic traits. Based on eQTL information and other variant annotations (distance from target gene transcript, minor allele frequency, and chromatin state), we created multivariate logistic regression models to predict SNP membership in reported GWAS. The complete model revealed independent contributions of specific annotations as strong predictors, including evidence for an eQTL (odds ratio (OR) = 1.2–2.0, P < 10−11) and the chromatin states of active promoters, different classes of strong or weak enhancers, or transcriptionally active regions (OR = 1.5–2.3, P < 10−11). This complete prediction model including eQTL association information ultimately allowed for better discrimination of SNPs with higher probabilities of GWAS membership (6.3–10.0%, compared to 3.5% for a random SNP) than the other two models excluding eQTL information. This eQTL-based prediction model of disease relevance can help systematically prioritize non-coding GWAS SNPs for further functional characterization.
Etiology of bacterial vaginosis and polymicrobial biofilm formation

Abstract Microorganisms in nature rarely exist in a planktonic form, but in the form of biofilms. Biofilms have been identified as the cause of many chronic and persistent infections and have been implicated in the etiology of bacterial vaginosis (BV). Bacterial vaginosis is the most common form of vaginal infection in women of reproductive age. Similar to other biofilm infections, BV biofilms protect the BV-related bacteria against antibiotics and cause recurrent BV. In this review, an overview of BV-related bacteria, conceptual models and the stages involved in the polymicrobial BV biofilm formation will be discussed.
Evolving Choice Inconsistencies in Choice of Prescription Drug Insurance

We study choice over prescription insurance plans by the elderly using government administrative data to evaluate how these choices evolve over time. We find large "foregone savings" from not choosing the lowest cost plan that has grown over time. We develop a structural framework to decompose the changes in "foregone welfare" from inconsistent choices into choice set changes and choice function changes from a fixed choice set. We find that foregone welfare increases over time due primarily to changes in plan characteristics such as premiums and out-of-pocket costs; we estimate little learning at either the individual or cohort level.
Effects of resveratrol on drug‐ and carcinogen‐metabolizing enzymes, implications for cancer prevention

Resveratrol is a polyphenol found in grape skins and peanuts that has demonstrated many health benefits including protection against aging, cardiovascular and metabolic disease, neurological decline, and cancer. The anticancer properties of resveratrol have been attributed to a variety of mechanisms, including its general inhibition of phase I metabolism and induction of phase II metabolism. The effects of resveratrol on these enzymes, however, are still unclear, as in vitro evidence often contrasts with animal studies and clinical trials. Reasons for these variances could include the low bioavailability of resveratrol and the effects of resveratrol metabolites. Due to resveratrol's interactions with drug‐metabolizing enzymes and drug transporters, individuals concurrently taking pharmacological doses of resveratrol with other supplements or medications could potentially experience nutrient‐drug interactions. This review summarizes the known effects of resveratrol and its main metabolites on drug metabolism in order to help characterize which populations might benefit from resveratrol for the prevention of cancer, as well as those that may need to avoid supplementation due to potential drug interactions.
Incidence and outcomes of cerebrovascular events complicating catheter ablation for atrial fibrillation.

AIMS Cerebrovascular complications are relatively uncommon, but severe adverse events are associated with catheter ablation of atrial fibrillation (AF). This study aimed to investigate the incidence, risk factors, and hospital outcomes of cerebrovascular events complicating AF ablation. METHODS AND RESULTS Cerebrovascular complications occurring during the procedure or hospitalization after AF ablation were assessed. Cerebrovascular events occurred in 9 of 1946 consecutive procedures (0.46%). Seven patients (0.36% per procedure) were diagnosed with ischaemic stroke and two patients (0.1% per procedure) with intracranial haemorrhage (ICH). Six events (6/9, 66.7%) occurred during the ablation and the remainders within 24 h after the ablation. Multivariable analysis revealed that previous ischaemic stroke [odds ratio (OR) 10.549; 95% confidence interval (CI) 2.551-43.625, P = 0.001] and mechanical valve replacement (OR 3.261; 95% CI 1.337-7.953, P = 0.009) were independent predictors. In a separate model, CHA2DS2-VASc score ≥3 (OR 7.992; 95% CI 2.046-31.215, P = 0.003) and mechanical valve replacement (OR 4.104; 95% CI 1.644-10.245, P = 0.002) were significantly associated with cerebrovascular complications. All patients survived to discharge except the two cases with ICH. CONCLUSION Cerebrovascular complications related to catheter ablation of AF are relatively infrequent and typically occur early either during the procedure or within the first 24 h after AF ablation. Previous ischaemic stroke, mechanical valve replacement, and CHA2DS2-VASc score ≥3 are independent predictors of such complications. The majority of these events are ischaemic stroke with a benign clinical outcome, while ICH may correlate with poor prognosis.
Ecology of tern flight in relation to wind, topography and aerodynamic theory

Flight is an economical mode of locomotion, because it is both fast and relatively cheap per unit of distance, enabling birds to migrate long distances and obtain food over large areas. The power required to fly follows a U-shaped function in relation to airspeed, from which context dependent ‘optimal’ flight speeds can be derived. Crosswinds will displace birds away from their intended track unless they make compensatory adjustments of heading and airspeed. We report on flight track measurements in five geometrically similar tern species ranging one magnitude in body mass, from both migration and the breeding season at the island of Öland in the Baltic Sea. When leaving the southern point of Öland, migrating Arctic and common terns made a 60° shift in track direction, probably guided by a distant landmark. Terns adjusted both airspeed and heading in relation to tail and side wind, where coastlines facilitated compensation. Airspeed also depended on ecological context (searching versus not searching for food), and it increased with flock size. Species-specific maximum range speed agreed with predicted speeds from a new aerodynamic theory. Our study shows that the selection of airspeed is a behavioural trait that depended on a complex blend of internal and external factors. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’.
Gabapentin before laparoscopic sleeve gastrectomy reduces postoperative oxycodone consumption in obese patients: a randomized double-blind placebo-controlled trial.

BACKGROUND Postoperative pain can be prevented. Gabapentin may be effective in this role. Our primary objective was to test the hypothesis that a prophylactic administration of gabapentin in obese patients before surgery has an opioid-sparing effect and reduces postoperative oxycodone consumption more efficiently than placebo. METHODS The study enrolled 113 patients undergoing laparoscopic sleeve-gastrectomy under general anesthesia. The patients were randomly allocated to the control or gabapentin group and received a single oral dose of gabapentin 1200 mg or a matching placebo 1 h before surgery. RESULTS The mean time from the end of anesthesia to the commencement of analgesic therapy was 74.3±37.8 minutes in the placebo group and 110.4±65.4 minutes with gabapentin (mean difference: -36, 95% CI: 12 to 40, P=0.0004). The mean 12-hour oxycodone consumption was 31.5±10 mg with placebo and 26.3±10 mg with gabapentin (mean difference: -5.2 mg, 95% CI: -9.08 to -1.35, P=0.0085). The mean NRS pain intensity at 12 hours was 2±0.9 in the placebo group and 1.5±0.9 with gabapentin (mean difference: -0.5, 95% CI: 0.15 to 0.81, P=0.003). CONCLUSIONS The demand for oxycodone was delayed in the gabapentin group; also, the total 12-hour dose requirement of oxycodone was lower in the gabapentin group.
Choice Inconsistencies among the Elderly: Evidence from Plan Choice in the Medicare Part D Program: Reply.

We explore the in- and out-of-sample robustness of tests for choice inconsistencies based on parameter restrictions in parametric models, focusing on tests proposed by Ketcham, Kuminoff, and Powers (2016). We argue that their nonparametric alternatives are inherently conservative with respect to detecting mistakes. We then show that our parametric model is robust to KKP's suggested specification checks, and that comprehensive goodness of fit measures perform better with our model than the expected utility model.Finally, we explore the robustness of our 2011 results to alternative normative assumptions highlighting the role of brand fixed effects and unobservable characteristics.
Attribute reduction based on maximal rules in decision formal context

AbstractOne of the key issues in the theory of concept lattices is to extract the useful rules from the decision formal context. The maximal rules implicate the others, thus people are interested in them. This paper proposes two new kinds of attribute reduction in the decision formal context based on maximal rules. The reducts preserve all the condition extensions and the decision extensions related to the original maximal rules. The internal relationship between the original maximal rules and the maximal rules in the reduced decision formal context is derived. The reducts can make the maximal rules more concise and accurate. The mathematical property of the proposed attribute reduction is investigated and we construct the discernibility matrix and function to compute all the reducts. Finally, all the attributes are classified into three types based on the maximal rules. The characteristics of these types of attributes are also analyzed.
Genetics of Parkinson disease

During the past decade five genes have been identified that are important in autosomal dominant and autosomal recessive forms of Parkinson disease. The identification of these genes has increased our understanding of the likely pathogenic mechanisms resulting in disease. However, mutations in these genes likely contribute to disease in fewer than 5% of all cases of Parkinson disease. Thus, researchers have continued to search for genes that may influence disease susceptibility. Molecular diagnostic testing is currently available for four of the genes mutated in Parkinson disease. Evidence for reduced penetrance, possible effects of haploinsufficiency, and the identification of nondisease causing polymorphisms within several of these genes has made genetic counseling challenging. Current recommendations are to limit molecular testing only to those individuals who are symptomatic. Furthermore, because treatment is unaltered by the presence or absence of mutations in these genes, restraint is recommended when considering the value of screening for mutations in a clinical setting.
A matching pursuit algorithm for inferring tonic sympathetic arousal from spontaneous skin conductance fluctuations

Abstract Tonic sympathetic arousal is often inferred from spontaneous fluctuations in skin conductance, and this relies on assumptions about the shape of these fluctuations and how they are generated. We have previously furnished a psychophysiological model for this relation, and an efficient and reliable inversion method to estimate tonic arousal from given data in the framework of dynamic causal modeling (DCM). Here, we provide a fast alternative inversion method in the form of a matching pursuit (MP) algorithm. Analyzing simulated data, this algorithm approximates the true underlying arousal up to about 10 spontaneous fluctuations per minute of data. For empirical data, we assess predictive validity as the ability to differentiate two known psychological arousal states. Predictive validity is comparable between the methods for three datasets, and also comparable to visual peak scoring. Computation time of the MP algorithm is 2–3 orders of magnitude faster for the MP than the DCM algorithm. In summary, the new MP algorithm provides a fast and reliable alternative to DCM inversion for SF data, in particular when the expected number of fluctuations is lower than 10 per minute, as in typical experimental situations.
A Pause-then-Cancel model of stopping: evidence from basal ganglia neurophysiology

Many studies have implicated the basal ganglia in the suppression of action impulses (‘stopping’). Here, we discuss recent neurophysiological evidence that distinct hypothesized processes involved in action preparation and cancellation can be mapped onto distinct basal ganglia cell types and pathways. We examine how movement-related activity in the striatum is related to a ‘Go’ process and how going may be modulated by brief epochs of beta oscillations. We then describe how, rather than a unitary ‘Stop’ process, there appear to be separate, complementary ‘Pause’ and ‘Cancel’ mechanisms. We discuss the implications of these stopping subprocesses for the interpretation of the stop-signal reaction time—in particular, some activity that seems too slow to causally contribute to stopping when assuming a single Stop processes may actually be fast enough under a Pause-then-Cancel model. Finally, we suggest that combining complementary neural mechanisms that emphasize speed or accuracy respectively may serve more generally to optimize speed–accuracy trade-offs. This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Aldehyde oxidase: an enzyme of emerging importance in drug discovery.

David C. Pryde,* Deepak Dalvie, Qiyue Hu, Peter Jones, R. Scott Obach, ) and Thien-Duc Tran WorldWide Medicinal Chemistry, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, England, Pharmacokinetics, Dynamics andMetabolism, Pfizer Global Research andDevelopment, 10628 ScienceCenterDrive, La Jolla, California 92121, WorldWide Medicinal Chemistry, Pfizer Global Research and Development, 10628 Science Center Drive, La Jolla, California 92121, and ) Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340
Energy-Based Water Droplet Impact Erosion Studies of Laser-Treated Austenitic and Martensitic Steels and their Applications

High-power diode laser (HPDL) surface treatments of high-manganese austenitic and high-chromium martensitic steel round specimens have been carried out, and their resistance to water droplet impact erosion (WDIE) in air was evaluated as per ASTM G73-10, Standard Test Method for Liquid Impingement Erosion Using Rotating Apparatus. This is because the water droplets always travel along with a fluid medium, either steam or air, and these are influenced by inertial, Coriolis, and centrifugal forces, which are missing in a vacuum. Because of these forces, the water droplets elongate and may break before hitting a target, resulting in WDIE damages entirely different from those in a vacuum. The WDIE damages on the test specimens were observed on the leading edge towards the suction side, where the boundary layer is attached, and the pressure gradients are high. These are similar to those occurring on the blades of an axial flow compressor of a gas turbine, a low-pressure steam turbine, and a helicopter rotor, because their leading edges are round. The WDIE testing is based on water droplet kinetic energy (KEd) and kinetic energy flux (KEfd). It has been proved experimentally that the product of KEd and KEfd can predict WDIE damages in a material, and this product can be used to compare the WDIE test results of different materials received from different laboratories. It is observed from the test results that the resistance to WDIE of HPDL-treated high-manganese austenitic steel (Hadfield’s steel) has reduced drastically, whereas that of high-chromium martensitic stainless steel has improved manifold. Fine microstructure and increased martensitic contents in high-chromium martensitic stainless steel after HPDL treatment are the main reasons for its improved performance, whereas the coarse microstructure having microcracks in HPDL-treated Hadfield’s steel is responsible for poor performance.
Experiences of caring for a family member with Parkinson's disease: a meta-synthesis

ABSTRACT Objective: The aim of this qualitative meta-synthesis was to search and then synthesise family caregivers’ experiences of providing care to individuals with Parkinson's disease (PD). Method: A systematic search resulted in the identification of 11 qualitative studies. Noblit and Hare's seven-stage approach was used to provide a higher-order interpretation of how family caregivers’ experienced the effects of taking on a caregiving role. Results: The process of reciprocal translation resulted in four overarching themes: (1) the need to carry on as usual – ‘the caregiver must continue with his life’; (2) the importance of support in facilitating coping – ‘I'm still going back to the support group’; (3) the difficult balancing act between caregiving and caregiver needs – ‘I cannot get sick because I'm a caregiver’; (4) conflicts in seeking information and knowledge – ‘maybe better not to know’. Conclusion: The themes reflected different aspects of family caregivers’ lives that were affected as a result of caring for a relative diagnosed with PD and these raise challenges for more simplistic theories of family caring and appropriate support structures. The findings also highlight several recommendations for clinical practice.
Clustering Based on Gaussian Processes

In this letter, we develop a gaussian process model for clustering. The variances of predictive values in gaussian processes learned from a training data are shown to comprise an estimate of the support of a probability density function. The constructed variance function is then applied to construct a set of contours that enclose the data points, which correspond to cluster boundaries. To perform clustering tasks of the data points, an associated dynamical system is built, and its topological invariant property is investigated. The experimental results show that the proposed method works successfully for clustering problems with arbitrary shapes.
Genetic Analysis of a Population Heavy Drinking Phenotype Identifies Risk Variants in Whites

Abstract Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1–5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals—Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)—and in a separate cohort of related individuals —Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 × 10−05) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 × 10−05) and rs9839267 near cholecystokinin (P = 3.05 × 10−05) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.
Multi-Objective Optimization of Bi-Layer Metallic Sheet Using Pareto-Based Genetic Algorithm

The bi-layer materials have been used widely during past decades due to their specific characteristics like lighter weight, more corrosion resistance, and insulation features in comparison with mono-layers which consisting them. In this research the aim is achieving to best combination of bi-layer material (Al3105-St14) to satisfy two objectives of weight and formability while it has a constant total thickness. The represent the formability objective and is derived from M-K model associated with Barlat-Lian yield criteria. Another objective is weight of per unit area. The data of experiments are designed based on full factorial method and the surfaces are best polynomial which can fit the variables and objectives. The MATLAB software and the genetic algorithm (GA) are used to generate feasible combination of thickness to provide to minimize the weight and maximize the formability. The Pareto frontier is utilized to satisfy two objective functions simultaneously. The best answer is selected with norm approaching and minimum distance method.